Recent Advances in the Synthesis of C -oligosaccharides...Recent Advances in the Synthesis of C-oligosaccharides Current Topics in Medicinal Chemistry, 2005 , Vol. 5, No. 14 1395 Enone

Current Topics in Medicinal Chemistry 2005 5 1393-1430 1393

1568-026605 $5000+00 copy 2005 Bentham Science Publishers Ltd

Recent Advances in the Synthesis of C-oligosaccharides

Xuejun Yuan and Robert J Linhardt

Department of Chemistry and Chemical Biology Rensselaer Polytechnic Institute Troy NY 12180 USA

Abstract This paper reviews the recent advances in the synthesis of catabolically stable sugar mimetics C-oligosaccharides These compounds are synthetic analogs of the naturally occurring O-oligosaccharides in which theinterglycosidic oxygen has been replaced by a methylene group This review is organized in terms of chemistry used toassemble C-oligosaccarides under the sub-headings anionic approaches cationic methods reductive glycosyl samariumchemistry cyclization methodology and free radical chemistry

1 INTRODUCTION

Oligosaccharides (oligo means few in Greek) arecomposed of 2 to 10 glycosidically-linked mono-saccharides[1] Oligosaccharides are hydrolyzed readily by aqueous acidto form an oligosaccharides constituent monosaccharidesOligosaccharides represent a unique class of glycosides inwhich the ldquoaglyconrdquo is also a carbohydrate residue instead ofa simple alcohol

Oligosaccharides and glycocojugates are involved in amultitude of biological processes including cell recognitioncell differentiation and cell adhesion In addition a numberof protein-carbohydrate interactions mediate critical biologicalprocess such as cell signaling in growth and differentiationand fertilization [2] While these above processes aregenerally beneficial carbohydrates also play major roles in anumber of detrimental processes including inflammationviral and bacterial infections and tumor metastasis Majorachievements in the development of carbohydrate basedtherapeutics include the synthesis of a heparin penta-saccharide which displays selective antithrombic activityand the design and synthesis of derivatives of sialyl Lewis Xantigen that are interest as potential anti-inflammatoryagents [3]

However the glycosidic bonds connecting individualsaccharides units within carbohydrate-based therapeutics areunstable to mild acid and to glycosidase enzymes in vivothus agents with enhanced stability need be developed [4]Considerable research has focused on the synthesis of C-glycosides stable mimics of the naturally occurring O-saccharides These molecules in which the interglycosidicoxygen has been replaced by a methylene group can beconsidered as chemically inert isosteres of natural O- and N-glycosides and are stable to mild acid in vitro andglycosidase enzymes in vivo [5]

C-Oligosaccharides are defined as compounds with twoor more sugar units linked by one carbon atom through(1rarr1) (1rarr2) (1rarr3) or (1rarr4) linkages or linked by twocarbon atoms for (1rarr1) or (1rarr6) linkages Syntheticallyprepared C-glycosides have so far proved useful for probing

Address correspondence to this author at Department of Chemistry andChemical Biology Rensselaer Polytechnic Institute Troy NY 12180 USAE-mail linharrpiedu

stereoelectronic effects which can control the conformationof oligosaccharides and can also prevent viral and bacterialattachment to lectins in adhesion assays to the same extentas O-glycosides [6] C-glycosides can inhibit some carbo-hydrate processing enzymes Oligosaccharides and glyco-conjugates are biosynthesized through complicated highlyefficient enzyme mediated routes The structure of the finalglycoconjugate is governed by the action of a series ofenzymes Alteration in the regulation of these enzymes isbelieved to be responsible for the biosynthesis ofcarbohydrates associated with disease processes Inhibitorsof glycosidase and glycosyltransferase enzymes are currentlyreceiving attention as new pharmaceutical agents Moreovera number of enzyme inhibitors have proven therapeuticefficacy for the treatment of diseases such as influenza andAIDS [7]

Biological studies have shown that the natural inhibitorshighlighted in Fig 1 exert their effects on a range ofglycosidases and are therefore of limited use as medicinalagents [8] Consequently more specific inhibitors arecurrently being sought that can be engineered to moreaccurately resemble the substrates that they are mimickingand thereby provide greater selectivity Early tests on C-glycosides have provided evidence for their potential to actas oligosaccharide processing inhibitors [7]

Fig (1) Natural inhibitors

The area of C-linked glycoside synthesis has beenextensively reviewed over the past 15 years [9] The

HON

HOOH

HONH

HO

OHOH

HONH

HOOH

OH

N

HOH

A

OH

Castanospermine(Glucosidase I and II)

Deoxynojrimycin (Glucosidase I)

Deoxymannojirimycin (Mannosidase)

Swainsonine(Mannosidase II)

1394 Current Topics in Medicinal Chemistry 2005 Vol 5 No 14 Yuan and Linhardt

organization of this review is based on the type of chemistryused to assemble the target C-oligosaccharides The chemistryinvolved includes anionic and cationic chemistry reductivesamariation cyclization methodology and free radicalapproaches Methods that afford the C-oligosaccharides withhigh stereoselectivity at the anomeric center (α or β) areclearly desirable This selectivity can be controlled by eitherstarting with a stereochemically defined C-glycoside whichis then coupled with another sugar or by controlling thestereochemistry of the newly formed center

2 ANIONIC APPROACHES

21 Enolate Anions

Fraser-Reid and Jarosz coupled two monosaccharideunits through a directed aldol reaction [10] Aldehyde 1 wasdeprotonated with (Me3Si)2NLi (LiHMDS) to give thechelated enolate 2 which was condensed with aldehyde 3 togive 4a as the major product (Scheme 1)

The zinc-copper-mediated reaction between 5 and 6 givesrise to the generation of single product 7 in 78 yielddemonstrating a remarkable double stereoselectivity with astrong preference for α-C-glycosylation of the ulosyl bromide

together with the elaboration of the (R) configuration for theCHOH group linking the pyranoid moieties (Scheme 2) [11]

Vogel utilized a ldquonaked sugarrdquo approach for the synthesisof an aza-C-disaccharide Enolate derived from 8 wascoupled with aldehyde 9 to give the adduct 10 in 61 yieldThe ketone was reduced and the resulting diol wasacetylated This was followed by selenoxide elimination toafford olefin 11 which was converted to 12 as shown inScheme 3 [12]

Cross-aldol reaction of racemic aldehyde 14 with enan-tiomerically pure lithium enolate of (-)-(1R4R5R6R)- or (-)-(1S4S5S6S)-13 results in mixtures composed mostly ofenantiomerically pure (+)-15 and (-)-15 respectively in 37-48 (only one of the isomers is shown in Scheme 4) [13]

Vogel and co-workers use a novel approach to C-disaccharide synthesis that involves conjugate addition andenolate trapping [14] Levoglucosenone 16 was treated withMe2AlSPh to give the aluminium enolate 17 Condensationof 17 with aldehyde 18 gave the aldol product that wasreduced with DIBAL to 20 Treatment of 20 with acidicmethanol afforded the (1rarr3)-C-disaccharide 21 (Scheme 5)

Scheme (1)

Scheme (2)

OO

OOBn

CHO

LiHMDS

5R

OO

OOBn

OHC

O

OBn OMe

OBn

OBn

C

OH6R

OO

OBnO

CHOLi

5S

OO

OOBn

OHC

O

OBn OMe

OBn

OBn

C

OH

O

OBn OMe

OBn

OBn

CHO

6S

+

1 2 3

4a 4b

O

O

Br

OBz

BzO

BzO

OO

O

O

O

O

O

O

OBz

BzO

BzO

OH

O

O

O

OO

5

1 Zn-Cu THF -35degC

2 NaHCO3

6

7 78

Recent Advances in the Synthesis of C-oligosaccharides Current Topics in Medicinal Chemistry 2005 Vol 5 No 14 1395

Enone 22 was synthesized and condensation of trappingenolate with aldehyde 23 led to a mixture of aldols 24 and 25that were separated by column chromatography on silica geland isolated in 15 and 29 yield respectively Reductionof the major aldol 25 with NaBH4 in MeOHTHF was highlystereoselective and provided the C-disaccharide 26 in 77yield (Scheme 6) [15]

When reacted with PhMe2SiZnMe2Li in THF at -78 ordmCenone 27 afforded a single adduct 28 Treatment of ketone28 with dicyclohexylboron chloride and Et3N at -15 ordmCfollowed by addition of 29 the resulting aldol-borate wasoxidized with 35 H2O2 giving adduct 30 in 24 yieldStereoselective reduction of aldol 30 with Me4NBH(AcO)3

afforded diol 31 in 59 yield (Scheme 7) [15]

22 Nitro Stabilized Anions

Vasella and Martin pioneered the use of nitro-basedanions for C-saccharide synthesis Anomeric nitro derivative32 was treated with TBAF and exposed to aldehyde 33 togive the adduct 34 in 78 yield Acetylation of 34 followedby reductive denitration afforded 35 (Scheme 8) [16]

Martinrsquos work has also relied on the Henry reactionAldol condensation of nitro sugar 36 with aldehyde 33 gave37 Dehydration of 37 and conjugate reduction led to 38Removal of nitro group by radical-based reduction followedby the removal of protecting groups gave rise to the (1rarr6)-β-C-disaccharide 40 (Scheme 9) [17]

Scheme (3)

Scheme (4)

NCbz

BnO

O

O

O

Cl

OAc

OAc

NCbzBnO

OO

O

PhSe

Cl O

OH

NCbz

CHO

OBnO

O

HO

N

OBn

OAc

CO2Me

AcO

OMe

CbzOMe

OAc OAc

O

PhSe

Cl OTHF -95 o C

1 NaBH42 Ac2O Pyr3 mCPBA

1 SOCl2 MeOH2 Ac2O Pyr3 Me3NO OsO44 Ac2O Pyr5mCPBA

LiHMDS -78 oC

8

9

10

1112

O

BnO

TBSO

O

OBnO

BzO

OBz

Br

CHO

OTIPS

O

BnO

TBSO

O

OBnO

BzO

OBz

Br

OTIPS

OH1 LiHMDS

2

1315

14


Scheme (5)

Scheme (6)

OO

O

Me2AlSPh OAlMe2O

O

SPh

O

OH

O

O

OO

O

OH

SPh

OH

O

HO

HO

OMeOH

OMe

HO

O

O

SPhO

O

O

OO

H

HO

HO

OO

O

SPhO

O

OO

HOH

DIBAL

MeOHTsOH

50 o C

16 17

18

19

2021

OO

bull

OR

O

CHOOMe

OO

NaBH4

OOH

bull

OR

OOMe

OO

OH

OO

bull

OR

OOMe

OO

HO

OO

bull

OR

OOMe

OO

OH

Me2AlSPh -78 degC

R = (t-Bu)Me2Si

22

23

24 15

+

25 2926 77


Scheme (7)

Scheme (8)

An open chain sugar derived aldehyde was used to accessa C-trehalose derivative through the Henry reactionCondensation of 36 with aldehyde 41 in the presence of KFand crown ether 18-crown-6 gave adduct 42 which wasimmediately converted to 43 with a sequence of reactions in29 overall yield The intermediate was finally transformedto the C-linked-(1rarr1)-disaccharide 44 (C-ββ-trehalose)(Scheme 10) [17]

Martin and coworkers applied the same methodologyto prepare an OC-trisaccharide namely methyl O-β-D-glucopyranosyl-(1rarr4)-C-β-D-glucopyranosyl-(1rarr6)-D-

glucopyranoside 48 [18] The condensation of compound 45with 6-aldehydo-glucopyranoside 46 in the presence of KFin an aprotic medium afforded the desired pseudotri-saccharide 47 in 73 yield Application of the samechemistry to 47 gave the target compound 48 (Scheme 11)

Kobertz and coworkers utilized Martinrsquos methodology toprepare C-allolactose Nitro sugar 49 was condensed withaldehyde 50 afforded the adduct 51 as a mixture ofdiastereomers The hydroxyl group was converted to thecorresponding phenyl thiocarbonate ester 52 Treatment withtin hydride and a radical initiator effected elimination

OO

OR OR

O SiMePh

O

HO

PhMe2SiZnMe2 Li

O

TBSO

TBSO

OTBS

OTBS

H

O

O

OR

SiMePh

TBSO

OTBS

OTBS

OH

HOHO

TBSO

O

O

TBSO

TBSO

OTBS

OTBS

OH

H

O

OR

SiMePh

Me4NBH(OAc)3

R = (t-Bu)Me2Si

+

1 THF -78 oC

2 NH4Cl H2O

3 HCl H2O 20 oC

1 (c-hex) 2BCl Et3N

2

27

28

29

30 24 over 2 steps31 59

O

O

O

O O

NO2

TBAF

O

OH

OO

OO

O

O

OO O

NO2

OO

O

OO

OH

O

O

OO O

OO

O

OO

H

OAc

32

3334 78

1 Ac2O Pyr2 Bu3SnH AIBN

35 89


reaction yielding only E-olefin 53 Finally the olefin wasreduced with dimide (generated in situ) and benzyl etherswere removed by dissolving metal reduction to afford thetarget disaccharide 54 (Scheme 12) [19]

Gurjar et al synthesized the first methyl α-C-D-araf-(1rarr5)-α-D-araf 60 the C-disaccharide segment of motif Cof Mycobacterium tuberculosis through nitro-aldol conden-

sation The coupling reaction between 55 and 56 gavediasteromeric mixture 57 which was subjected to threesubsequent steps ie dehydration selective reduction ofconjugated olefin and denitration to give the penta-O-benzylC-disaccharide 59 (Scheme 13) [20]

Witczak has used nitro anions for C-disaccharidesynthesis Michael addition of the nitro anion derived from

Scheme (9)

Scheme (10)

OAcO

AcOOAc

OAc

NO2O

OH

O

O

OO

OHO

HOOH

OH

O

HO

HOOH

OH

Bu3 SnH

OAcO

AcOOAc

OAc

NO2

OO

O

OO

OH

OAcO

AcOOAc

OAc

X

OO

O

OO

KF 18-C-6 MeCN

1 Ac2O Pyr2 NaBH4 EtOH

38 X = NO 2

39 X = H 57

1 NaOMe

2 H3O+

36

33

37

40 89 over 2 st eps

CHO

O

O

O

O

CH2OPiv

OAcO

AcOOAc

OAc

NO2

OHO

HOOH

OH

O OH

OH

HO

OH

OAcO

AcOOAc

OAc

NO2

PivO

OH

O

O

O

O

OAcO

AcOOAc

OAc

NO2

PivO

O

O

O

O

1 Ac2O Pyr2 80 AcOH3 Ac2O Pyr

1 AcOH

2 Ac2O-BF3 OEt

KF 18-C-6 MeCN

41 36

42

4344

3 Bu3SnH AIBN

4 NaOMe

5 H3O+


61 to levoglucosenone 62 gave adduct 63 in 43 yield Thesterics in 62 dictates the facial bias of the addition whichcan only occur from the α-face Reductive denitrationfollowed by reduction of lactol and ketone afforded 64 Ringopening deprotection and acetylation gave 65 (Scheme 14)[21]

23 Sulfur Stabilized Anions

The Taylor group employed the Meyers variant of theRamberg-Baumlcklund reaction to synthesize C-disaccharides[22] The penta-O-benzyl thioglucose 66 was coupled withiodide compound 67 followed by oxidation of the formedsulfide gave sulfone 68 Exposure of the sulfone to theMeyers variant of the Ramberg-Baumlcklund reaction affordedexo-glycal 69 as a mixture of isomers in 48 yieldHydrogenation of this mixture stereoselectively reduceddouble bond and cleaved the benzyl groups Peracetylated C-

trehalose 70 was furnished by acetylation of free sugar(Scheme 15)

This approach is well suited to analog synthesis simplyby varying the alkylating agent Thus the homologous(1rarr1rsquo)-C-disaccharide containing a two-carbon bridge(ldquohomoisotrehaloserdquo) was readily prepared (Scheme 16)[23] Lactol 71 was converted into sulfonate 74 by astraightforward three-step sequence involving Moffat-typeC-glycosylation to give ester 72 followed by reduction andmesylation Next 74 was coupled with thiol 75 in a similaralkylation-oxidation sequence to that above The resultingsulfone 77 underwent a halogenative Ramberg-Baumlcklundrearrangement (RBR) to give exo-glycal 78 as a 8812mixture of (Z)- and (E)-isomers in 57 yield Subsequentreductiondebenzylation followed by acetylation producedthe novel ethylene-bridged disaccahride 79

Scheme (11)

Scheme (12)

OBnO

OBnOMe

BnO

NO2

OBnO

OBn

BnO

OBn

CHO

OHO

OH

HO

OH

OHO

OHOMe

HO

OBnO

OBn

BnO

OBn

OBnO

OBnOMe

BnO

NO2R

OBnO

OBn

BnO

OBn

OBnO

OBnOMe

BnO

KF 18-C-6 MeCN+

1 n-BuLi2 PTC-Cl

51 R = OH

52 R = OC(S)OPh

Bu3 SnH AIBN

1 TsNHNH NaOAc

2 Na NH3

49

50

5354

OAcO

OAc

AcOO

OAcO

OAc

OAc

NO2OAc

OAc

AcO

OAcO

BnOOBn

OMe

BnO

OO

AcOOAc

OAc

OAcO

OMe

BnO O

BnOOBn

O

OO

AcOOAc

OAc

NO2

OAcO

OAc

AcO

OAcO

BnOOBn

OMe

BnO

OH

KF 18-C-6 MeCN

1 Ac2O Pyr2 NaBH4 EtOH3 Bu3SnH AIBN4 H2 Pd(OH)2

5 NaOMe MeOH

45

46

47

48


This group also reported a rapid synthesis of a range ofC-disaccharides involving a tandem Horner-Wadsworth-Emmons (HWE)conjugate-addition C-glycosylation followedby a tandem halogenation-RBR sequence utilizing Meyersvariant of the RBR [24] The HWE reagent 81 proceeded theHWEconjugate-addition sequence with diisopropylidenemannofuranose 80 in 86 yield to produce the adductsulfone 82 (as a mixture of diastereomers) The keyhalogenation-RBR was carried out using the conditions

devised by Chan et al giving E-alkene 83 as the onlyisolable product Alkene hydrogenation and concomitantdebenzylation followed by acetylation for characterizationpurposes gave the novel disaccharide 84 in 69 yield overthe two reactions (Scheme 17)

A two-directional variant of this methodology can beused to prepare symmetrical C-disaccharides as shown inScheme 18 [24] The double HWE reaction on diisopro-pylidene mannofuranose 80 worked extremely well in the

Scheme (13)

Scheme (14)

BnO

OBn

O2N

OMe

O

CHO

OBnO

OBn

BnO

OMe

OHO

OH

OHO

OH

HO

OMe

OBnO

OBn

OBnO

OBn

BnO

HO

NO2

OMe

OBnO

OBn

OBnO

OBn

BnO

X

+

KF 18-C-6 MeCN


58 X = NO 2

59 X = H 44 over 3 st eps

Bu3SnH AIBN

Pd(OH)2 H2

rt 1 atm 24 h

40

60 74

55

56

57

O

BnOOBn

BnO

OBn

OH

O

OHNO2

O

O

BnOOBn

BnO

OBn

OH

O

ONO2

O

O

O

O

O

AcOOAc

AcO

OAc

O

OAc OAc

OAc

O

BnOOBn

BnO

OBn

NO2OH

Et3 N MeCN

1Bu3 SnH AIBN

2 BF OEt Et3SH

3 L-SelectrideTHF

64 61 in 3 steps

1 Pd(OH)2 C6 H10

2 Ac2O TESOTF

61 63 43

62

65


HWEconjugation-addition C-glycosydation sequence givingdiastereomeric sulfones 85 in a combined yield of 75RBR of the major stereoisomer (βα-79) using the Meyers-

Chan procedure gave alkene 86 in 66 unoptimized yieldand hydrogenation produced the novel C-linked bisfuranosedisaccharide 87 in 76 yield

Scheme (15)

Scheme (16)

OBnO

BnO

H

OBn

OH

OOBn

BnO

OBn

OBn

BnO

OBn

OBn

OBnO

BnO

OBn

OH

SO2

O

OBn

O O

AcO

AcO

AcO

OAc

OAc

OAc

OAc

OAc

OBnO

BnO

OBn

OH

I

O

HS

OBn

BnO

OBn

OBn

68 90 over 2 steps

KOH CCl4 t-BuOH H2O

1 H2 PdC

2 Ac2O Pyr

70 69 over 2 steps

+

1 K2CO3

2 mCPA66

67

69

O

BnOOBn

BnO

OBn

OH

(EtO)2P(O)CH2CO2Et

OBn

OBn

OBnO

OBn

OBnO

BnOOBn

OBn

X

O OBn

OBn

BnOOBn

OBnO

BnOOBn

OBn

OBnO

BnOOBn

OBn

R

OBnO

BnOOBn

OBn

SH

LiAlH4

OAc

AcOOAc

O OAcOAcOAcO

OAc

OAc

1 H2 Pd(OH)2C

2 Ac2 O Pyr

NaH THF

72 R = CO2Et

73 R = CH2OH

66 over 3 steps

K2CO3 acetone

76 X = S

77 X = SO2 79

Oxone THF MeOH H2 O

KOH CCl4 aq tBuOH

78 57ZE 8812

79

71

75

MsCl Et3N 74 R = CH2 OMs


Norris et al deprotonated 88 with n-BuLi and theresulting anion was coupled with an excess lactone 89 at lowtemperature to afford the adduct 90 in 77 yield SPhgroups were removed with Raney nickel and lactol 91 wasisolated as a syrup that contained two components in

approximately a 41 ratio The two compounds were thoughtto be α- and β-lactols with the latter being major It wasstraightforward to reduce the lactols with a high degree ofstereocontrol to afford the C-disaccharide 92 with a 51isolated yield (Scheme 19) [25]

Scheme (17)

Scheme (18)

O

O O

O

O OH

O OMe

OBnBnO

SO2

P

EtO

EtO

O

OBn

O

OMe

OAc

OAc

OAcO

O O

O

O

O

OO OMe

OBnBnO

SO2

OBn

O

O O

O

O O

O

O

O

OMe

OBn

OBn

OBn

83 50 E only

80

+

NaH THF -78 oC

82 86αβ 11

KOHAl2O3

CBr2F2 CH2Cl2

tBuOH 5 oC

2 h

1 H2PdC EtOAc RT 7h

2 Ac2 O Pyr RT

84 69 over 2 st eps

81

O

O O

O

O OH POEt

OEt

O

SO2

P

EtO

EtOO

O

O

O

OO

O

O

O

O O

O

O

O O

O

O

O

O SO2

O

O

O

O

O

O O

O

OO

O

O

85 75βαββ ca 31

86 66β αββ = 141 E only

H2PdC EtOAc

87 76βαβ β = 141

21 NaH THF -78 o C

80 (2 equiv)

KOHAl2O3CBr2F2 CH2Cl2tBuOH

on majorβα is omer


24 Phosphorous Stabilized Anions

The most common type of reaction discussed in thissection is Wittig approach to C-oligosaccharide synthesisThis methodology is particularly suited for synthesis of(1rarr6)-C-saccharides since one sugar can hold the aldehydewhile the other the ylid or phosphonate anion

Dondoni has utilized this approach to prepare a variety ofβ-D-(1rarr6)-C- disaccharides The general approach is shownin Scheme 20 Coupling of β-linked galactopyranosyl ormannofuranosyl derivative (93 94 95 or 96) with ylidefrom phosphonium iodide 97 or 98 gave alkene 99 Alkenewas reduced and removal of deprotecting groups gave thecorresponding β-D-(1rarr6)-C- disaccharide 100 [26]

α-D-(1rarr6)-C-disaccharide 103 was also synthesizedusing the approach (Scheme 21)

Dondoni applied this methodology in an iterative fashionto prepare the corresponding β-(1rarr6)-C-trigalactosides andβ-(1rarr6)-C-tetragalactosides [27] Starting with coupling ofylide 104 generated in situ with aldehyde 33 gave adduct105 (EZ 19) Removal of silyl protecting group followed byoxidation led to aldehyde 106 which was coupled with theylide from 104 to give C-trisaccharide 107 in 36 yield Thesame sequence was repeated with 107 afforded the protectedC-tetrasaccharide alkene 108 Compounds 108 wasdesilylated and exposed to hydrogen over Pd(OH)2 oncarbon followed to peracetylation gave protected C-tetrasaccharide 109 (Scheme 22)

Taking advantage of their experience on the stereo-selective synthesis of C-oligosaccharides by iterative Wittigolefination this group developed new building blocks and amodified protocol for the straightforward assembly of C-α-(1rarr5)-D-oligoarabinofuranosides [28] While the twomonofunctionalized sugar moieties 110 and 111 weresuitable precursors to the head and tail of the oligo-saccharidic chain the difunctionalized compound 114 was arepeating unit (Scheme 23) Building block 114 wasdesigned to allow after the Wittig coupling for regenerationof the formyl group in a single step under conditions that donot affect the chemical and stereochemical integrity of thegrowing saccharidic chain (Scheme 24)

Colinas et al reported a method for the synthesis of C-disaccharides by a sequence involving the Wittig reaction askey step and further glycosydation of these compounds toafford new C O-trisaccharides [29] The enol ether 122a-bwere prepared by the Wittig reaction of the α β mixture of2-deoxiglycosyl phosphonium salts 120a-b with aldehyde121 Hydrogenation of the exo-glycals afforded the β-C-disaccharides with good yields The O-glycosidationemploying the exo-glycals and the glycosyl acceptor 124 isillustrated in Scheme 25

25 C-1 Vinyl Anions

Schmidt was the first to explore the addition of sulfoxide-stabilized vinyl C-1-organolithiums to carbohydrate-basedcarbonyl compounds [30] The vinyl sulfoxide 126 was

Scheme (19)

OCH3

O O

OPhS

PhS

O O

OO

OCH3

O O

OO O

O H

OCH3

O O

OPhSPhS

O O

O OH

OCH3

O O

OO O

O OH

+

n-BuLi THF -78 oC

Raney Ni EtOH H2O rt

Et3SiH BF3 OEt2

90 77

92 51 over 2 steps 91 is omers rati o βα = 41

-78 oC

88

89


deprotonated with LDA to give 127 Addition of 127 toaldehyde 128 gave a mixture of diastereoisomers of whichthe major 129 was formed in a 101 ratio Desulfurizationhydroboration and removal of benzyl groups gave the(1rarr5)- βminusC-disaccharide 130 (Scheme 26)

Schmidt and coworkers used this methodology for ahighly efficient synthesis of an analog of C-trehalose 134Scheme 27 [31] Anion 131 was converted to aldehyde 132

and condensation of this aldehyde with the same anion gaveadduct 133 which was then converted to the target C-disaccharide 134

26 Acetylide-Based Anions

Sinayuml was the first to prepare a C-disaccharide Hisapproach involved the coupling of a C-6 alkyne with ananomeric lactone followed by reduction of the formedhemiacetal [32] Aldehyde 135 was converted to the

Scheme (20)

Scheme (21)

OO O

O

O CHO

O

BnOOBn

BnO

OBn

CHO

OBn

CHO

BnO

O

BnOBnO

O

BnOOBn

BnO OBn

CHO

PPh3I-

OO

O

OO

O

OMeOBn

OBn

OBn

PPh3I-

OCHO

O

PPh3I-

ORRO

RO

OO

ORRHO

OO

OR

+ +

+

( 93 - 96 )

( 97 - 98 )

BuLi THF-HMPA

-30 iexclaelig

99

Reduction

100

+

93 9495

96 97 98

O

OBnBnO

BnO

OO

O

OO

HO

O

O

OO

PPh3I-

O

OHHO

HO

O

HOOH OH

HO

OBnBnO

CHO

BnO

O

+

BuLi THF-HMPA

-30 oC

1 p-MeC 6H4SO2-

NH2NH2 AcONa

2 H2 Pd(OH)2 3 bar

3 Amberli te H+

+

10197

102

103


dibromoalkene 136 which was treated with n-butyllithium togive an intermediate acetylide 137 The latter uponnucleophilic addition to lactone 138 gave a mixture of lactol139 in high yield Stereoselective reduction of lactol 139 wasfollowed by hydrogenation of benzyl groups and the triplebond affording the (1rarr6)-β-C-disaccharide 140 (Scheme28)

The lactone-addition methodology was later applied bySinayuml and co-workers in an iterative fashion for the

preparation of higher homologues [33] Hydroxylmethylenein compound 141 was converted to acetylide lithium incompound 142 by a sequence of reactions Condensation ofcompound 142 with the galacto lactone 143 gave 144 asmixture of anomers The lactol were stereoselectivelyreduced to and triple bond was hydrogenated to give 145Methyl glycoside 145 was hydrolyzed to the correspondinglactols which were oxidized to lactone 146 The samesequence was then repeated twice to give C-trisaccharide147 and C-tetrasaccharide 148 (Scheme 29)

Scheme (22)

O

BnOOBn

BnO OTBDPS

PPh3I-

BnO

H

O

BnOOBn

OTBDPS

OO

O

OO

O

CHOO

O

OO

O

BnO

O

BnOOBn

BnO

OO

O

OO

H

HOBn

BnO OTBDPS

O

BnOOBn

BnO O

OO

O

OO

H

OBn

BnO OTBDPS

PPh3I-

O

BnO

O

BnOOBn

BnO OTBDPS

PPh3I-

O

AcOOAc

AcO

O

AcOOAc

AcO

OO

O

OO

O

AcOOAc

AcO OAc

O

BnOOBn

BnO

O

BnOOBn

BnO

OO

O

OO

H

H

O

BnOOBn

BnO OTBDPS

H

1 TBAF2 PCC

+107 36

+

1 TBAF2 PCC3

+

1 TBAF2 H2 Pd(OH)2 C3 Ac2 O Pyr

104

33

105

106104

104

108109

BuLi THF-HMPA

-50 o C

70EZ 19

BuLi THF-HMPA

-50 o C


The di- tri- and tetrasaccharide derivatives (145 147 and148) were all debenzylated and tested for their bindingaffinity to three different monoclonal immunoglobulins withspecificity for different O-β-(1rarr6)-D-galactopyranosyl deter-minants These C-saccharide analogs had similar bindingproperties to the corresponding O-saccharides

Schmidt has also used acetylide-lactone condensation toassemble C-disaccharides of ketoses [34] Lithium acetylide149 was condensed with ketone 150 to give a mixture ofalcohol 151 after removal of the pivoloyl group Attemptedcyclization under Lewis acid catalysis resulted only in theremoval of the acetonide Accordingly the diol was tiedback as the carbonate and the acetylene complex as thedicobalt species 152 The isomers were then separately

cyclized to give a 11 mixture of C-disaccharide 153 Thecobalt complex on α-C-disaccharide was removed understandard conditions to give 154 and deprotection of thecarbonate was followed by hydrogenation and peracetylationto give 155 (Scheme 30) Similar chemistry was also carriedout with the corresponding β-isomer

Van Boom and co-workers used lithiated alkynylderivative 156 in presence of ZnCl2 to selectively open ringof the 12-anhydrosugar 157 affording the α-C-(alkynyl)-glycoside 158 Hydrogenolysis of the benzyl groups wasfollowed by peracetylation to give the (1rarr6)-α-C-disaccharide 159 (Scheme 31) [35]

Normally attack of the nucleophile proceeds from anequatorial direction to give the β-isomer The unexpected

Scheme (23)

Scheme (24)

BnOO

OBnCHO

OBn

O

OBn

PPh3I-

OBn

OBn

O

OBn

BnOBnO

O

OBnOBn

OBnH

O

OH

HOHO

O

OHOH

OH+

BuLi

THF-HMPA

-20 oC+

1 TBAF2 H2 Pd(OH)2C

112 65 113 100

110

111

O

OBnCHO

OBnBnO

O

OBn

BnOBnO

O

OBnCH(OiPr)2

OBnH

O

OBnCH(OiPr)2

PPh3I-

OBn

O

OBn

BnOBnO

O

OBn

OBnH

O

OBnOBn

BnOH

O

OH

HOHO

O

OH

OH

O

OHOH

HO

++

BuLi

THF-HMPA

-20 oC

BuLi

THF-HMPA

-20 oC

TFA H2 O THF rt

115 49

116 R = CH(OiPr)2

117 R = CHO

118 45

H2 Pd(OH)2C

110

114

114

119


Scheme (25)

Scheme (26)

OBn

R1

R2

PPh3BF4-O

O

OOHC

O

O

O

O

O

O

O

O

HO

O

O

O

O

O O

OBn

R1

R2

O

O

O

O

O

O

H

O

OBn

R1

R2

O

O

O

O

O

O

O

O

OBn

R1

R2

O

O

O

+

BCl3 (005 equiv)

MS 4A CH2 Cl2 0 o C

+

BuLi THF -90 oC -90 o C

to rtH2 (1 atm) PdC Et3N MeOH

R1 R2 = OBn H

120a - b

121

122a - b

123a - b

124

125a - b

OTBDPS

BnO X

SO Ph

O

BnO

OHCO

BnO

OMeOBn

OBn

O

BnO

OTBDPS

BnO

SO Ph

O

BnO

OMeOBn

OBn

O

HO

OMeOH

OHO

HOHO

OH

OH

128

229 74

1 RaNi (74)

2 BH3 DMS

NaOH H 2O2 (74)

3 H2 PdC (70)

130 74

LDA THF

-100 oC

126 X = H

127 X = Li


Scheme (27)

Scheme (28)

stereochemical outcome is rationalized by the generation ofan initial zinc acetylide species which facilitates intra-molecular delivery to the α-face (Scheme 32)

Wightman synthesized C-disaccharide analogs of the α-D-arabinofuranosyl-(1rarr5)-α-D-arabinofuranosyl motif ofmycobacterial cell walls through alkynyl intermediates [36]The lactone 164 was treated with lithio(trimethylsilyl)ethyneat low temperature to give lactol in 66 yield of 165Treatment of this with triethylsilane and BF3

Et2O gavethe separable isomers 166α (60) and 166β (13)Desilylation of the major isomer 166α gave 167 in 97yield Treatment of 167 with n-BuLi followed by addition oflactone 164 gave 85 yield of the hemiacetal 168 which onreduction with Et3SiH and BF3

Et2O gave the disubstitutedalkyne 169 (83) as the major product Reduction-

hydrogenolysis of 169 then gave the C-disaccharide 170 innear-quantitative yield (Scheme 33)

3 REDUCTIVE GLYCOSYL SAMARIUM SPECIES

The introduction of SmI2 as reducing agent can becredited to Kagan and has since been utilized in numeroussynthetic schemes [37] Sinayuml and Beau introduced SmI2

chemistry into C-glycoside synthesis through intermolecularreactions with appropriate electrophiles and intramolecularreactions of silyl tethered substrates [38] Anomericsamarium species are highly stable and not likely to undergoβ-elimination Treatment of the aryl sulfone 171 with SmI2

affords the nucleophilic intermediate 172 through two singleelectron transfer processes Introduction of a suitableelectrophile (carbonyl compounds) affords the α-C-manno-

O

BnO

OTBDPS

BnO X

SO Ph

O

BnO

OBn

BnO Li

SO Ph

DMF

OHO

HOOH

OH

O OH

OH

HO

OHOH

O

BnO

OTBDPS

BnO

SO Ph

O

OBn

OBnOBnSO

Ph

OH

131 X = Li

132 X = CHO

THF -100 oC

1 Ra-Ni

2 BH3 DMS NaOH H2O2

3 H2 PdC

131

133

134

OBnO

OBnOMe

BnO

Li

OBnO

BnOOBn

OBn

OOBn

OBnOMeBnO

OH

OBnO

BnOOBn

OBn

O

n-BuLi

BnO

OMe

BnO

BrBr

O

OBn

OHO

OH

OH

HO

OHO

OH

HO

OMe

O

BnO

OMeOBn

O

BnO

139 92

1BF3 OEt2 EtOH

2 H2 PdC AcOH

140 52 over 2 steps

135 136 137

138

CBr4 PPh3


pyrannoside 173 in good yield and with excellent stereo-selectivity (Scheme 34) [38a]

Preparation of C-glycosides of ulosonic acids using SmI2

was pioneered by Linhardt and coworkers [39] Coupling ofpyridyl sulfone 174 with aldehyde 175 in the presence ofSmI2 gave an excellent yield of the N-acetylneuraminic acidC-disaccharide 176 as single isomer This stereochemicaloutcome was rationalized on the basis of the Felkin-Anhmodel for predicting the stereochemical outcome of akinetically controlled addition of a nucleophile to a chiraladehyde (Scheme 35 A)

Reductive samarium method was utilized to synthesizesialo-antigen C-analogs by the Linhardt group A fullyprotected C-analogue of the SialylTn antigen α-D-Neu5Ac-(2rarr6)α-D-GalNAc-(1rarrO)-Ser 182 was prepared [40] C-glycosylation of the neuraminic acid sulfone donor with

aldehyde acceptor in presence of excess SmI2 afforded the α-C-glycoside 180 as an RS mixture (11) The criticalintermediate aldehyde acceptor 178 was prepared in 13steps Chemoselective resolution to compound 180 wasundertaken by oxidation with DMSOAc2O to keto-bridgedcompound 181 followed by stereoselective reduction withZn(BH4)2 to regenerate the bridge hydroxyl function gave182 in gt90 de (Scheme 36)

A common versatile N-acetylneuraminic acid C-disaccharide precursor of the C-glycoside analogs ofgangliosides GM4 and GM3 has been synthesized [41]Samarium(II) iodide coupling of N-acetylneuraminic acidsulfone 179 with a 3-formyl galactopyranoside derivative183 afforded the corresponding C-disaccharide 184 as amixture of (R) and (S) isomers at the newly formedhydroxymethylene bridge This diastereoisomeric mixturewas resolved after debenzylation of the galactoside residue

Scheme (29)

O

BnO

BnOOBn

OBn

OOBn

OBnOMe

OBnOH

O

BnO

BnO

OBn

OBn

O

O

BnOOBn

OMe

BnO

Li

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnOBnO

OBn

OBnBnO

O

BnO

BnO

OBn

O

OBnO

OBn

OBnBnO

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OMe

1 PCC2 CBr4 Ph3P3 n-BuLi

144 overall yield 54

1 BF3 OEt2 Et3 OH

2 H2 PtO2 EtOAc

145 76

1 H2 SO4 AcOH

2 PCC

146 62

repeat steps

repeat st eps

141 142

143

147

148


Scheme (30)

Scheme (31)

O

BnOOBn

OMe

Li

BnO

OPivBnO

OBn

OBn

BnO

O OO

BF3 OEt2

OBnO

OBn

OBn

BnO

OO

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

CAN

OBnO

OBn

OBn

BnO

OO

OO

BnOOBn

BnO

OMe

OHBnO

OBn

OBn

BnO

OHO

O

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

OPivBnO

OBn

OBn

BnO

OH OO

O

OMe

BnOOBn

BnO

OAcO

OAc

OAc

AcO

OAcOAc

OAcO

OAc

AcO

OMe

1

2 NaOMe MeOH

1 Lewis acid2 ClCO2CCl3 Pyr3 Co2(CO)8

with a-isomer

1 Et3N Pyr H2O

2 H2 PdC H+

3 Ac2 O Pyr

149 151

152153

154 155

150

OBn

BnO

OBnO

OBn

BnO

OBnO

BnO

MeO

OBnO

OBn

BnO

O

OMe

AcO

OAcO

OAc

OAc

AcO

OAcO

OAc

O

BnOOBn

OMe

BnO

159 74 over 2 steps

+

BuLi ZnCl2 THF

1 H2 PdC2 Ac2O Pyr

156 157

158 59


Scheme (32)

Scheme (33)

and the chirality of each isomer assigned after acetylationConversion of the p-methoxyphenyl group in the peracety-lated (S) isomer 187 into the corresponding thiophenylglycoside 188 was accomplished affording the key inter-mediate for the synthesis of C-glycoside analogs of GM4GM3 and other related gangliosides (Scheme 37)

Ganglioside GM4 is a very important cell adhesionmolecule The C-disaccharide of GM4 is currently beingsynthesized in Linhardtrsquos lab using standard O-glycosylationof C-disaccharide with protected ceramide Once theceramide has been attached it can be oxidized to afford analdehyde group for coupling to keyhole limpet hemocyanin

OBnO

OBn

BnO

O

OBnO

ClZnO

OBn

BnOCl

R

OBnO

O

OBn

BnOCl

ZnR

O

ZnR

OBnO

OBn

BnO

160 161

162163

O

OBn

OBnBnO

O

O

OBn

OBnBnO H

TMS

O

OBn

OBnBnO H

O

OBn

BnO

OBnHO

O

OBn

OBnBnO OH

TMS

OBnBnO HO

OBn

TMS

O

OR

ORRO H

O

OR

RO

OR

OBn

OBnBnO

H

TMS

O+

K2CO3 MeOH

1 n-BuLi THF -78 oC

2 164

164165 66

166α 60 166β 13167 97

BF3 Et 2O Et 3SiH -78 oC

168 85

169 R = Bn 83

170 R = H near quantitative yield

H2 (1 atm)Pd(OH) 2C

TMS-acetyl ene

n-BuLi THF -78 oC BF3 Et2O Et3SiH

-78 o C


O

OHCOBn

OBnBnO

OMe

O

CO2MeAcO

OAcAcHN

OAc

SO2

NAcO

OBnH

H

OBn

OBn

H

O

OMeH HH

A

O

CO2MeAcO

OAcAcHN

OAc

O

OBnOMe

OBnOBn

HO

AcO

+

Nu

174175

176

SmI2 THF

Scheme (34)

Scheme (35)

Scheme (36)

O

BnO

BnO

BnO

Si lylO

O2S N

O

BnO

HO R2R1

BnOBnO

SilylO

OBnO

BnO

BnO

SilylO

Sm(III)

R1COR2 SmI2 THF

171 172

173

NHBoc

OAcO

AcO

AcHN O

O

CO2BnO

OO

OO

OH

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

R2

O

CO2Me

AcHN

OAc

AcO

R1

AcO

AcO

AcHNO CO2Bn

NHBoc

AcO

OAc

O

Zn(BH4)2

180 R1 R2 = H OH ( RS 11)

181 R1 R2 = O

182 R1 = H R2 = OH de gt 90

DMSO Ac2O

177178

179

13 steps

22 equiv SmI2 THF


Scheme (37)

Fig (2)

(KLH) by reductive amination for use as carbohydrate-basedvaccine GM3 a related trisaccharide containg gangliosideplays an important role in cell growth and differentiationFig 2 The synthesis of C-oligosaccharide GM3 is currentlyunderway following a similar route to that of C-GM4synthesis [42]

Beau also reported a sialyl C-disaccharide synthesiswhich relied on the unprecedented use of a stable andcrystalline 2-pyridyl sulfide of the N-acetylneuraminic acidderivative 189 as the anomeric precursor in a samarium-Reformastky procedure [43] The coupling procedure withsulfide 189 and aldehyde 190 afforded the carbon-linkeddimer 191 in 93 yield as a 11 diastereomeric mixture

Alcohols 191 were converted into thiocarbonates anddeoxygenated by employing triphenyltin hydride catalyticAIBN and pentafluorophenol which yielded C-disaccharide192 as a single compound in 65 yield for the 2 stepsDesilylation hydrogenolysis acetylation and finalacetolysis of the methyl glycoside provided the carbon-linked mimic 193 of the disaccharidic component of thesialylTn tumor antigen (Scheme 38)

4 CATIONIC METHODS

This section is categorized according to reactions thatinvolve the generation of anomeric ions followed by thecapture with sugar-based nucleophiles

OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO

H2 PdC EtOAc CH3OHH2O

+

Ac2O Pyr

187 X = OMP

188 X = SPh 73

184 85 R and S mixture

186 90 for two i somers

+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3


41 Exo-glycals as Nucleophiles

Nitotra et al have found that treatment of exo-glycal 194with BF 3

OEt2 followed by a water quench afforded the C-disaccharide 195 (Scheme 39) It is noteworthy tonoteworthy that the attack of the enol ether on the anomericoxonium ion occurs with high stereoselectivity on the α-face only 195 was obtained [44]

42 Silyl-based Nucleophiles

Isobe has designed and developed alkynylation as a keyreaction for the introduction of a carbon chain onto sugarsThose alkynylated compounds are called ldquosugar acetylenesrdquo[45] The mechanism includes eliminative formation ofcation to which silylacetylene can coordinate on the α-face(Scheme 40)

Double C-glycosylation between glycal 198 and bis(silylacetylene) gave C-disaccharide ldquolikerdquo compounds 199and 200 (Scheme 41)

Silylpropargyl-sugar 201 smoothly reacted with D-glucalto furnish exclusively the α-acetylene glycoside product 202in 88 (Scheme 42) [46]

5 CYCLIZATION METHODOLOGY

This approach to C-oligosaccharide synthesis relies onthe coupling of an open chain fragment with an intact

monosaccharide to give an intermediate that is then cyclizedto deliver the C-oligosaccharide target This section isdivided by the type of chemistry used to initially assemblethe two pre-cyclization fragments

51 Wittig Reaction-Cyclization

The Kishi group was the first to use Wittig-cyclizationapproach to synthesize C-disaccharides Starting with Wittigreaction between 203 and 204 the intermediate 205 wasafforded as a single stereoisomer in 82 yield Osmylationthen gave a mixture of diols with the major one formed in a61 ratio Selective protection of the diols gave 206a and206b The mono-para-methoxybenzyl ether 206a was thentransformed into the hemiketal 207 in 75 overall yield inthree steps ie (1) Swern oxidation (2) acetonide hydro-lysis (4 N HClTHFrt) and (3) benzoylation (3 equiv ofPhCOClpyCH2Cl2rt) Silane reduction of 207 in an acidicmedium should preferentially yield the equatorially substi-tuted β-C-glycoside which was deblocked and converted tothe methyl- βminusC-disaccharide 209 Exact parallel experi-ments applied to the minor isomer gave the correspondingC-disaccharide 210 (Scheme 43) [47]

Armstrong has employed Wittig-osmylation protocol forthe preparation of a small library of α-C-(1rarr6)-disaccha-rides [48] Readily available allyl C-glycoside 211 washomologated to diene ester 212 and subjected to osmylation

Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65

1 MeOHHCl2 H2 PdC EtOH3 Ac2O Pyr4 Ac2OAcOHH2SO4

193 59 overall yield

25 equiv SmI2 THF

1 11-thiocarbonyldiimidazole DMAP2 Ph3SnH cat AIBN

191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61

1 Swern [O]2 4N HCl3 PhCOCl pyr


1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210


followed by reduction to afford a 51 mixture (213214215216) of lactols that were readily separable by chromato-graphy Following a deprotection of an equimolar mixture of213 and 214 217 and the DL hybrid C-disaccharide of D-glucose-O-(1rarr6)-L-galactose 218 were obtained The DDand DL derivatives 219 and 220 of glucose-α-(1rarr6)-idosewere also obtained as a near equimolar mixture afterdeprotection of 215 and 216 (Scheme 44)

52 Anion Addition-Cyclization

Kishi developed an approach for the synthesis of theCndashtrehalo sugars which relied on nucleophilic addition ofone intact sugar fragment to a fundamental aldehyde ieKishi-Nozaki reaction [49] Coupling of monosaccharide221 and aldehyde 222 gave 223 The triple bond waspartially reduced and osmylation was followed by selectiveprotection to afford 224 The acetonide was converted toepoxide 225 by standard methods and removal of the PMBgroup Acid-catalyzed cyclization followed by aglyconichydrolysis and protection of hydroxyl group with (p-methoxyphenyl)diphenylmethyl chloride (MMTrCl) gave226 Inversion of the C-2 hydroxyl and removal of protectinggroups delivered α α-C-trehalose 227 (Scheme 44)

Kishi and co-workers also employed aldol reactions as anefficient access to the C-trisaccharide related to the type IIABO(H) blood group determinant [50] Aldol condensationof the enolate of methyl ketone 228 with aldehyde 229 gavea 41 mixture of hydroxy ketones 230 and 231 The majorketol was cyclized desulfurized and oxidized to afford thedisaccharide ketone 233 The ketone in THF was treatedwith LiHMDS (3 equiv) and TMEDA followed by theaddition of MgBr2 Addition of the aldehyde 234 led toalmost exclusive formation of the equatorial products 235and 236 in a 12 ratio Mesylation of 235 and 236 followedby treatment with liquid ammonia gave enones 237a and237b which were reduced to yield exclusively the C-2rsquo-equatorial ketone 238 Sodium borohydride reduction of theC-3rsquo carbonyl proceeded with the desired stereoselectivity toyield the protected C-trisaccharide 239 which wasdeblocked to provide the polyol 240 (Scheme 46)

Sutherlin and Amstrong cleverly applied a recursivestereochemical deconvolution (RSD) combinatorial approachfor the synthesis of a small library of C-trisaccharides aspotential inhibitors for the cell surface proteins of bacteriumHelicobactor pylori [51] The workers chose to carry outvariations in galactose ring of these trisaccharides An

Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220

1 9-BBN H2O22 Swern [O]

3 t-BuOK

4 I2 C6H6212

211


efficient Nozaki-Kishi coupling of vinyl bromide 241 withaldehyde 242 in a diasteromeric ratio of 12 followed byprotection with TBSOTf led to 243 and 244 Hydroborationfollowed by oxidation gave aldehydes 245 and 246respectively Addition of allylmagnesium bromide toaldehyde 245 followed by removal of the silyl groupafforded 247 to 246 giving 248 and 249 Epoxidation gave a11 mixture of the corresponding epoxides which werecyclized to give the C-trisaccharide 250-255 after removalof the benzyl groups (Scheme 47)

Schmidt reported a stereoselective 6-exo-trig selectiveelectrophilic cylization approach for de novo synthesis of amethylene-bridged Neu5Ac-α-(23)-Gal C-disaccharide theC-analog of an important motif in glycosphingolipids [52]The open chain precusors 259ab (a 32-mixture ofdiaseteromeric alcohols) were formed by the addition oflithiated iodide 256 to open chain aldehyde 258 Subsequent

C1 incorporation using Tebbe-reagent formation of a cycliccarbonate and deprotection of the two isopropylidene ketalsafforded tetrol 264 which upon treatment with phenylselenyltrifilate was steroselectively cyclized in a 6-exo-trigselective manner affording a diasteromeric mixture of 251and 252 in a ratio of 71 A seleno-Pummerer rearrangementto afford aldehyde 267 in 5 steps in 90 overall yieldOxidation of the aldehyde and subsequent steps led to thedesired C-disaccharide 268 (Scheme 48)

53 Esterification-Cyclization

Work from the Postema group has focused on a ringclosing metathesis (RCM) approach for the synthesis of C-saccharides [53a] The chemistry is versatile and has beenused for the synthesis of a small library of differentiallylinked β-C-disaccharides through a radical allylation-RCMstrategy [53b] The synthesis of the β-(1rarr4)-glucopyranosyl

Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+

1 p-TsOH2 K2CO3 MeOH3 MMTrCl pyr

1 Swern [O]2 BH3 THF

3 AcOH-H2 O4 H2 Pd(OH)2

221

222

223

1 Pd-Pb CaCO3 H22 NaH BnBr3 OsO44 Bu2 SnO5 CsF PMB-Cl6 Ac2 O 4-DMAP

1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41

1 Bu3SnH AIBN2 Swern [O]

1 LiHMDS THF-TMEDA2 MgBr23

1 MsCl

2 liquid NH3

235 X = OH Y = H236 X = H Y = OH Bu3 SnH AIBN

237a and 237b

NaBH4 MeOH

238

239 X = OBn

240 X = OHH2 Pd(OH)2

229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242

1 CrCl2-NiCl2 T HF-DMF 722 TBSOTf 2 6-lutidine 91

243 244

1 9-BBN 602 Dess-Mart in period inane 97

1 9 -BBN 552 D ess-Martin periodinane 98

245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255

1 MCPBA2 CSA CH 2Cl2 61 fo r 2 steps3 H 2 Pd (O H)2C 95

1 MCPBA2 CSA CH 2Cl2 63 fo r 2 s teps3 H 2 Pd (OH)2C 87

1 MCPBA2 CSA CH2Cl2 80 for 2 steps3 H2 Pd(O H)2C 95


Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )

259ab (32) 79 com bine d yi eld

De ss-Ma rtin pe riodinane

260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t

264 quant it a ti ve yie ld

PhSe C l AgOT f

EtC N -80 oC

265

266

Quant it at i ve yi l ed 25 26 7 1

+

R =

1 Ac 2OPyr

2 mC PB A3 Ac 2ONa OAc

4 NaO HT HFMe OH

5 Ac2O P yr

267 90 overa ll yi e ld

ste ps

268


glucopyranoside 280 represents an example of thischemistry The known triacetyl glucopyranoside 269 wasconverted to iodide 270 in good yield Radical allylation of271 proceeded to afford a mixture of equatorial and axialallylation products in a 61 ratio Oxidative cleavage of thedouble bond gave the corresponding aldehydes 273a and273b which were separable Pinnick oxidation of the majoraldehyde 273a then gave the C-4 equatorial acid 274 DCC-mediated coupling of alcohol 275 and acid 274 proceeded toafford ester 276 in good yield Methylenation of 276 gave277 and exposure to catalysist 278 gave a 41 yield of theC-disaccharide glycal which was exposed to an excess ofBH3

THF to give 64 yield of the β-C-disaccharide 279Removal of the benzyl groups and global peracetylation gavethe peracetylated (1rarr4)-β-C-disaccharide 281 in good yield(Scheme 49)

54 Ring Expansion-Cyclization

Nelson developed a new strategy for asymmetric andstereoselective synthesis of C-linked disaccharide mimeticsthe C58-C71 fragment of palytoxin [54] The diol (RR)-282was converted into the di-dihydropyran (DHP) template 283284 and 285 The di-DHPs were functionized in a twodirectional sense using dihydroxylation reactions The two-directional approach was often very efficient indeed forexample in the synthesis of 286 six new stereogenic centerswere introduced with almost complete stereocontrol using areduction and a dihydroxylation reaction The approach isnot restricted to the synthesis of C2-symmetricaldisaccharide mimetics Using the unsymmetrical template285 which has both a pseudo-axial and a pseudo-equatorialhydroxyl groups the unsymmetrical mimetics 289 and 290were prepared (Scheme 50)

6 RADICAL APPROACHES

The radical approach for C-C bond formation is a popularmethod within organic chemistry The use of radicalchemistry in carbohydrate synthesis has certain advantagesFirstly the reaction conditions are very mild and tolerant ofa range of functional and protecting groups Secondanomeric radicals are stable with respect to elimination andepimeration Most significantly the chemistry required toincorporate an appropriate substitute at C-1 employed in theinitial hemolytic cleavage step is common within carbo-hydrate chemistry [55] The use of such radical techniquecan be subdivided into two classes intermolecular andintramolecular approaches

61 Intermolecular Radical Approaches

Giese was the first to employ an intermolecular radical-based approach for synthesis of C-disaccharides [56]Addition of an alkene to an anomeric radical underappropriate conditions allowed exclusive entry to the α-linked C-glycoside a result which was mirrored by the workof Baldwin [57] The high α-selectivity of the reaction wasin contrast with other reports Thus radicals generated at theC-2 C-3 and C-4 centers all preferred to occupy equatorialpositions [58] When the anomeric bromide 291 was treatedwith tin hydride and AIBN resulting anomeric radical andreacted with lactone 292 in a Michael addition it afforded293 In this reaction hydrogen abstraction at the resulting

radical center occurs from axial face to selectively generatethe equatorial C-2rsquo substituent Reduction and acetylation of293 furnished C-disaccharide 294 (Scheme 51) [59]

Witczak used the facial bias of levoglucosene tostereoselectively add a carbohydrate-based radical in thepreparation of the 3-deoxy-(1rarr4)-β-C-disaccharide 299[60] Addition of the radical derived from iodide 295 to 296gave adduct 297 in 26 yield Removal of the anomerichydroxyl of 297 was achieved by treatment with triethylsilane borontrifluoride ether complex followed bystereoselective reduction of the keto function at C-2rsquo withthe formation of 298 in 89 yield Debenzylation followedby acetolysis of 16-anhydro ring produced the peracetylatedtarget C-disaccharide 299 in 19 overall yield from 295(Scheme 52)

Vogel has developed general methods to transformenantiomerically pure 7-oxabicyclo[221]heptyl derivatives(ldquonaked sugarsrdquo) into C-disaccharides Because of thesechiral bicyclic skeletons they undergo highly stereoselectivereactions with predictable diasteroselectivities An arsenal ofmethods is available that allow to substitute these ldquonakedrdquocarbon centers with a variety of functional groups with allpossible relative configurations The methods allowpreparation of both enantiomers of a given target with thesame ease Predictably high stereoselectivity of the reactionsof the bicyclic chirons adds to the flexibility of approachwhich can lead to high molecular diversity [61]

α-C-(1rarr3)-mannopyranoside of N-acetyl-galactosaminepotent β-galactosidase inhibitors was synthesized by thisapproach [61] Enone 302 was readily prepared from 300The addition of the radical derived from bromide 303 toenone 302 afforded the αminusisomer 304 The ketone was thenreduced and the selenide eliminated via the intermediacy ofthe selenoxide to give 305 Acid-promoted (CF3SO3H) 7-oxa ring opening of 305 in MeCN produced the amino-conduritol derivative 306 resulting from the quenching of theallylic cation intermediate by the solvent (Ritter reaction)Ozonolysis of the chloroalkene 306 generated an acylchloride-aldehyde intermediate that reacted with MeOH toproduce a mixture of methyl uronates The major compound307 was silylated and reduced The crude polyol obtainedwas acetylated to produce 308 Desilylated and ammonolysisafforded a mixture of α-β-pyranoses 309 and correspondingα-β-furanoses (Scheme 53)

Similar chemistry was carried out to synthesize non-protected α-C(1rarr2)-L-fucopyranoside of D-galactopyrano-side corresponding to a blood group mimetic [62] Giesersquosradical fucosidation of racemic enone 310 with α-L-bromoacetofucose 311 provided the mixture of diastereo-meric α-C-fucoside 312a and 312b in reproducible yield of78 Reduction of the mixture gave a 11 mixture of endo-alcohols 313 and 314 which were isolated pure in 40 and355 yield respectively Oxidative elimination of thebenzeneselenyl group of 313 followed by acetylation gaveendo acetate 315 in 85 yield Acid-promoted ring openingof 315 and ozonolysis of the resulted chloroalkene gavemethyl uronic ester 316 in modest yield (10) Treatment of316 with Cl3CCN and NaH followed with BF3

OEt2

furnished the totally protected C-disaccharide 317 in 79


Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N

Mo C(Me2 Ph)((CF3)2 MeCO)2

O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93

271a X = CH2CH=CH2 Y = H R = Ac 64271b Y = CH2CH=CH2 X = H R = Ac 11272a X = CH2CH=CH2 Y = H R = Bn 75272b Y = CH2CH=CH2 X = H R = Bn 75273a X = CH2CHO Y = H R = Bn 79273a Y = CH2CHO X = H R = Bn 79

1 NaOMe MeOH2 NaOH BnBr DMF

OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51

TiCl4 Zn dust TMEDA CH2Br2PbCl2 (Cat )

1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286

1 VO(acac)2 t-BuOH 95

2 (MeO)3CH BF3 90

1 P-O2NC6H4 CO2H Ph3P DIAD2 K2CO3 MeOH 82 over 2 steps

1 PhCOCl Et3N DMAP 402 P-O2NC6H4 CO2H Ph3P DIAD3 KOH THF-H2O 75 over 2 steps

TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81

1 Na[Al(OC2H4OMe)2(OEt)H]2 Ac2O pyr

294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF

1 Pd(OH)2C C6H10 EtOH

2 EtSiOSO2CF3 Ac2O

298 89 over 2 steps299

296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH

1 (Me3Si)2NLi THF2 Me2N=CHI

1 Bu3 SnH AIBN2

1 NaBH42 mCPBA3 Ac2O pyr

1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3

1 TIPSOTf 26-lut idine2 LiBH43 Ac2 O pyr DMAP

furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309


The reduction of 317 and treatment with DOWEX-H+ resinprovided the desired C-fucoside 318 in 70 (Scheme 54)

62 Intramolecular Radical Approaches

One disadvantage with the intermolecular approaches isthat during such radical mediated reactions electrondeficient alkenes are required to facilitate C-C bondformation The intramolecular approach of Sinayuml overcomes

this drawback by bring two substrates together via atemporary covalent silaketal connector This enables the useof a wider range of alkenes which can include alkene-functionalized sugars thus leading to the generation of C-disaccharides [63] Based on the early work of Stork Sinayumlemployed the tether reaction in the synthesis of both α- andβ-C-disaccharides with this work subsequently beingemployed in the synthesis of biologically significant natural

Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+

1 NaBH4 MeOHTHF2 Chromatography

313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps


products [64] The availability of different hydroxyl groupson each monosaccharide unit allowed the fine-tuning ofstereochemical outcome by selective positioning of the silyltether [65] Development of this early stereochemical controlled to the tethering of the donor 320 with alcohol 319through a di-isopropyl silicon tether 321 Subsequent treat-ment with Bu3SnH and AIBN led to a 9-endo-trigcyclization to form the C-disaccharide 322 in an 80 yieldwith exclusive formation of the α-product The silyl tetherwas removed with Bu4NF and deprotection under standardconditions afforded the desired disaccharide 323 in excellentyield (Scheme 55)

In parallel the development of a 32rsquo silyl tether allowedaccess to the β-linked product as demonstrated in Sinayumlrsquossynthesis of methyl β-C-lactoside 328 [66] Alcohol 324 and320 were connected via the dimethylsilyl tether an 8-endo-trig cyclization followed to exclusively afford the β-

disaccharide 326 in 45 yield Removal of the tether anddeprotection of benzyl ether gave β-C-disaccharide 328(Scheme 56)

This group also selected iodosugars bearing a freehydroxyl group as progenitors of the radical donors [67] In atypical experiment the radical donor 329 was connected tothe radical acceptor 330 through a silaketal tether followingtheir procedure Tributyltinhydride mediated 8-endo-trigradical cyclization of compound 331 gave after detetheringof the non isolated intermediate 332 the protected β-C-disaccharide 333 in 37 overall yield (from startingmaterials 330 and 329) Peracetate 335 was achieved afterhydrogenolysis The C-laminaribioside 334 is of potentialbiological interest as it mimics the repeating disaccharideunit of fungal β-(1rarr3)-glucans which have antitumor andimmunomodulating properties (Scheme 57)

Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS

In this paper the biological importance of C-oligo-saccharides as subunits of natural products and as a newgeneration of carbohydrate based on therapeutics has beenillustrated Different methods are available for the synthesisof C-oligosaccharides As with traditional saccharidesynthesis it has been necessary to develop a number ofspecific approaches to facilitate the regioselective andstereoselective preparation of the desired targets Work inthis area continues and it is expected that many interestingnew C-oligosaccharides will be prepared using the chemistrydescribed in this review It is also likely that new chemistrywill be developed in the future for the preparation of thesebiologically important targets

ACKNOWLEDGEMENTS

The authors thank Dr Sultan Baytas for her criticalreading of this manuscript

REFERENCES

[1] Kennedy J F White C A Bioactive Carbohydrates InChemistry Biochemistry and Biology Ellis Horwood LtdChichesterUK 1983

[2] Wassarman PW Mammalian Fertilization Molecular Aspects ofGamete Adhesion xocytosion Exocytosis and Fusion Cell 199996 175-183

[3] Carbohydrate-based Drug Discovery Wong C-H EdWeinheim Cambridge Wiley-VCH 2003

[4] (a) Sharon N Lis H Lectins as Cell Recognition MoleculesScience 1987 246 227-234 (b) Dwek RA Chem Rev 1996 96683-720

[5] Postema M C-Glycoside synthesis CRC Boc Ratom 1995[6] (a) Weatherman R V Mortell K H Cheruenak MKiessling

L L Toone E J Specificity of C-Glycoside Complexation byMannoseGlucose Specific Lectins Biochem 1996 35 3619-3624(b) Ravishankar R Surolia A Vijayan M Lim S Kishi YPreferred Conformation of C-Lactose at the Free and Peanut LectinBound States J Am Chem Soc1998 120 11297-11303

[7] (a)Wong C-H Halcomb R L Ichikawa Y and Kajimoto TEnzymes in organic synthesis Application to the problems ofcarbohydrate recognition part2 Angew Chem Int Ed Engl 199534 521-546 (b)Howard S Withers SG Bromoketone C-Glycosides a New Class of βminusGlucanase Inactivators J AmChem Soc 1998 120 10326-10331(c) Wang Q Wolff MPolat T Du Y Linhardt R J C-glycoside of Neuraminic Acidsas Neura-minidase Inhibitors Bioorg Med Lett 2000 10 941-944 (d) Phili R Chang J Partis R A Mueller R A ChrestF J Passaniti A The Alpha-glucosidase I InhibitorCastanospermine Alters Endothelial cell Glycosylation PreventsAngiogenesis and Inhibits Tumor Growth Cancer Res 1995 552927-2935

[8] Ossor A Elbein A D In Carbohydrates in Chemistry andBiology Vol 3(II) WileyVCH 2000 pp 513-539

[9] (a) Sinayuml P Synthesis of oligosaccharide Mimetics Pure ApplChem 1997 69 459-463 (b) Beau J-M Gallagher TNucleophilic C-glycosyl Donors for C-glycoside Synthesis Top inCurr Chem 1997 187 1-54 (c) Nicotra F Synthesis of C-glycosides of Biological Interest Top in Curr Chem 1997 187

Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN

332 R1 R2 = SiMe2 R3 = Bn R4 R5 = CHPhTBAF THF

333 R1 = R2 = H R3 = Bn R4 = R5 = CHPh 37 from 11

334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331


55-83 (d) Du Y Linhardt R Y Recent Adv in Stereo-SelectiveC-Glycoside Synthesis Tetrahedron Lett 1998 54 9913-9959 (e)Liu L Mckee M and Postema M H D Synthesis of C-saccharides and Higher Congeners Current Org Chem 2001 51133-1167

[10] Jarosz S Fraser-Reid B Synthesis of A Higher Carbon Sugar ViaDirected Aldol Condensation Tetrahedron Lett 1989 30 2359-2362

[11] Lichtenthaler F W Lergenmiiller M Schwidetzky S C-Glycosidations of 2-Ketohexosyl With Electrophilic Radical andNudeophilic Anomeric Carbons Eur J Org Chem 2003 3094-3103

[12] Baudat A Vogel P Aza-C-disaccharides Synthesis of 6-Deoxygalactonojirimycin-β-C(1rarr3) Linked with D-Altrofuranosides and D-Galactose J Org Chem 1997 62 6252-6260

[13] Turner D Vogel P Synthesis of 4-Hydroxy-26-Bis(hydroxymethyl) tetrahydropyran-2-Carbaldehyde DerivativesSynlett 1998 304-306

[14] Zhu Y-H Vogel P Short Stereoselective Synthesis of C-(1rarr3)-Linked Disaccharides Tetrahedron Lett 1998 39 31-34

[15] Zhu Y-H Vogel P Synthesis of a (2R 6R)-2-(Hydroxymethyl)-6-Propa-1 2-Dienyl-2H-Pyran-3(6H)-One Derivative A NewEnone for The Convergent Construction of C-Glycosides of C-Disaccharides Synlett 2001 82-86

[16] Baumberger F Vasella A Deoxynitrosugars The 6th

Communication Stereolectronic Control in the reductivedenitration of tertiary nitro ethers A Synthesis of ldquoC-glycosidesrdquoHelv Chim Acta 1983 66 2210-2221

[17] Martin O R Lai W Synthesis and Conformational Studies of β-(1rarr6)- and ββ-(1rarr1)-Linked C-disaccharides J Org Chem1993 58 176-185

[18] Spak S J Martin R The synthesis of an analogue of Methyl OC-Analogue of Methyl 4rsquo-O-β-D-GlucopyranosylgentiobiosideTetrahedron 2000 56 217-224

[19] Kobertz W R Bertozzi C R Bednarski M D C-GlycosylAldehyde Synthons for C-Linked Disaccharides J Org Chem1996 61 1894-1897

[20] Gurjar M K Nagaprasad R and Ramana CV First Synthesis ofMethyl α-C-D-Arabino-furanosyl-(1rarr5)-αminusD-Arabinofuranosidethe C-Disaccharide Segment of Motif C of MycobateriumTuberculosis Tetrahedron Lett 2000 43 7577-7579

[21] Witczak Z J Synthesis of C-Glycosyl Compounds and OtherNatural Products from Levoglucosenone Pure Appl Chem 199466 2189-2192

[22] Griffin F K Paterson D Taylor R J K Ramberg-BacklundApproaches to the Synthesis of C-Linked Disaccharides AngewChem Int Engl 1999 38 2939-2942

[23] Paterson B E Griffin F K Alcaraz M-L and Taylor R J KA Ramberg-Baumlcklund Approach to the Synthesis of C-GlycosidesC-Linked Disaccharides and C-Glycosyl Amino Acids Eur JOrg Chem 2002 1323-1336

[24] McAllister G D Paterson D E Taylor R J K A SimplifiedRamberg-Bachlund Approach to Novel C-Glycosides and C-Linked Disaccharides Angew Chem Int Ed Engl 2003 42 1387-1391

[25] McCartney J L Christopher T M Cicchillo R M BernardinaM D Wagner T R and Norris P J Org Chem 2003 6810152-10155

[26] Dondoni A Zuurmond H M Bascarate A Synthesis of α-andβ-D-(1rarr6)-C-Disaccharides by Witting Olefination of Formyl C-Glycosides with Glycopyranose 6-phosphoranes J Org Chem1997 62 8114-8124

[27] Dondoni A Kleban M Zuurmond H Marra A Synthesis of(1rarr6)-C-Oligogalactosides by Interative Wittig OlefinationTetrahedron Lett 1998 39 7991-7994

[28] Dondoni A Marra A A New Synthetic Approach toMycobacterial Cell Wall α-(1rarr5)-D-Arabinofuranosyl C-Oligosaccharides Teterahedron Lett 2003 44 4067-4071

[29] Colinas P A Ponzinibbio A Lieberknecht A and Bravo R OWittig Reaction of Glycosyl Phosphonium Salts A StereoselectiveRoute to C-Disaccharides and C O-Trisaccharides TetrahedronLett 2003 44 7985-7988

[30] Schmidt R R Preuss R Synthesis of Carbon Tetrahedron Lett1989 30 3409-3412

[31] Dietrich H Schmidt R R Synthesis of Carbon-Bridged C-Lactose and Derivatives Liebigs Ann Chem 1994 975-981

[32] Rouzaud D Sinayuml P The First Synthesis of a ldquoC-DisacchariderdquoJ Chem Soc Chem Commun 1983 1353-1354

[33] Xin Y-C Zhang Y-M Mallet J-M Glaudemans C P JSinayuml P Synthesis of C-Oligosaccharides That Mimie TheirNatural O-Analogues Immunodeterminants in Binding toMonoclonal Immunoglobulins Eur J Org Chem 1999 471-476

[34] Streicher H Geyer A Schmidt R R C-Disaccharides ofKetoses Chem Eur J 1996 2 502-510

[35] Leeuwenburgh M A Timmers C M Vander Marel G A VanBoom J H Mallet J-M Sinayuml P G Stereoselective Synthesisof α-C-(Alkynyl)-Glycosides Via Ring-Opening of α-12-Anhydrous Tetrahedron Lett 1997 38 6251-6254

[36] Aslam T Fuchs M G G Le Formal A Wightman R HSynthesis of C-Disaccharide Analogue of the α-D-Arabinofuranosyl-(1rarr5)-α-Arabinofuranosyl Motif ofMycobacterial Cells Walls via Alkynyl Intermediates TetrahedronLett 2005 46 3249-3252

[37] (a) Girad P Namy J L Kagan H B Divalent LanthanideDerivative in Organic Synthesis 1 Mild Preparation of SamariumIodide and Ytterbium Iodide and Their Use as Reducing orCoupling Agents J Am Chem Soc 1980 102 2693-2698 (b)Molander G A Harris C R Sequencing Reactions withSamarium(II) Iodide Chem Rev 1996 96 307-338

[38] (a) Mazeacuteas D Skrydstrup T Doumeix O Beau J-MSamarium Iodide-Induced Intramolecular C-Glycoside FormationEfficient Radical Formation in the Absence of an Additive AngewChem Int Ed Engl 1994 33 1383-1386 (b) Mazeacuteas DSkrydstrup T Beau J-M A Highly Stereoselective Synthesis of1 2-trans-C-Glycosides Via Glycosyl Samarium(III) CompoundsAngew Chem Int Ed Engl 1995 34 909-912 (c) Jarreton OSkrydstrup T Beau J-M The Stereospecific Synthesis of Methylα-C-Mannobioside A Potential Inhibitor of M TuberculosisBinding to Human Macrophages J Chem Soc Chem Commun1996 1661-1662 (d) Jarreton O Skrydstrup T Espionosa J-FJimeacutenez-Barbero J Beau J-M Samarium Diiode Prompted C-Glycosylation An Application to The Stereospecific Synthesis ofα-(1rarr2)-C-Mannobioside and Its Derivatives Chem Eur J 19995 430-441 (e) Mipuel N Doisneau G Beau J-M ReductiveSamariation of Anomeric 2-Pyridyl Sulfones with Catalytic AnUnexpected Improvement in The Synthesis of 12-Trans-Diequatorial C-Glycosyl Compounds Angew Chem Int Ed Engl 2000 39 4111-4114

[39] Vlahov I R Vlahova P I Linhardt R J DiastereocontrolledSynthesis of Carbon Glycosides of N-Acetylneuraminic Acid ViaGlycosyl Samarium(III) Intermediates JAmChem Soc 1997 1191480-1481

[40] Kuberan B Sikkander S ATomiyama H Linhardt R JSynthesis of a C-Glycoside Analogue of sTn An HIV-and Tumor-Associated Antigen Angew Chem Int Ed Engl 2003 42 2073-2075

[41] Bazin H G Du Y Polat T Linhardt R J Synthesis of aVersatile Neuraminic Acid ldquoCrdquo-Disaccharide Precursor for theSynthesis of C-Glycoside Analogues of Gangliosides J OrgChem 1999 64 7254-7259

[42] Chen C-C Ress D K Linhardt RJ Samarium Iodide-Mediated Synthesis of Neuraminic Acid C-Glycosides InSynthesis of Glycommetics Roy R Ed ACS Syposium Series2004 896 53-80

[43] Abdallah Z Doisneau G Beau J-M Synthesis of a Carbon-Linked Mimic of The Disaccharide Component of The Tumor-Relate SialyTn Antigen Angew Chem Int Ed Engl 2003 425209-5212

[44] Lay L Nicotra F Panza L Russo G Caneva E Synthesis ofC-disaccharides through dimerization of exo-glycals J Org Chem1992 57 1304-1306

[45] Isobe M Nishizawa R Hosokawa S Nishikawa TStereocontrolled Synthesis and Reactivity of Sugar Acetylenes JChem Soc Chem Commun 1998 2665-2676

[46] Saeeng R Sirion U Sahakitpichan P Isobe M IodineCatalyzes C-Glycosidation of D-Glucal with SilylacetykeneTetrahedron Lett 2003 44 6211-6215

[47] (a) Babirad S A Wang Y Kishi Y Synthesis of C-Disaccharides J Org Chem 1987 52 1370-1372 (b) Wang YBabirad S A Kishi Y Preferred Conformation of C-Glycosides


8 Synthesis of 14-Linked Carbon Disaccharides J Org Chem1992 57 468-481

[48] Armstrong R W Sutherlin D P Strategies for the Synthesis ofC-Disaccharides Containing D and L Sugars Tetrahedron Lett1994 35 7743-7746

[49] Wei A Kishi Y Preferred Conformation of C-Glycosides 12Synthesis and Conformational Analysis of αα- α β- and β β-Trehaloses J Org Chem 1994 59 88-96

[50] Haneda T Goekjian P G Kim S H Kishi Y PreferredConformation of C-Glycosides 10 Synthesis and ConformationAnalysis of Carbon Trisaccharides J Org Chem 1992 57 490-498

[51] Sutherlin D P Armstrong R W Synthesis of 12 Stereochemistryand Structurally Diverse C-Trisaccharides J Org Chem 1997 625267-5283

[52] Notz W Hartel C Waldscheck B Schmidt R R De NovoSynthesis of a Methylene-Bridged Neu5Ac-α-(23)-Gal C-Disaccharide J Org Chem 2001 66 4250-4260

[53] (a) Postema M H D Calimente D Liu L Behrmanm T L AnOlefin Metathesis Route for the Preparation of (1rarr6)-Linked-C-Disaccharide Glycals A Convergent and Flexible Approach to C-Saccharide Synthesis J Org Chem 2000 65 6061-6068(b) Postema M H Piper J L Liu L Faust M Andreana PSynthesis and Partial Biological Evaluation of a Small Library ofDifferentially Linked β-C-Disaccharide J Org Chem 2003 684748-4754

[54] Nelson A The Development of Strategies and Methods for TheSynthesis of Biologically Active Compounds New J Chem 200428 771-776

[55] Togo H He W Waki Y Yokoyama M C-GlycosylationTechnology With Free Radiant Reactions Synlett 1998 700-717

[56] Giese B Dupuis J Diastereoselective Synthesis of C-Glycopyranosides Angew Chem Int Ed Engl 1983 22 622-623

[57] Adlington R M Baldwin J E Basak A Kozyrod RPApplication of Radical Addition Reactions to tho Synthesis of a C-Glucoside and A Functionalized Amino Acid J Chem SocChem Commun 1983 144-145

[58] Giese B Gonzaacutelez-Goacutemez J A Witzel T The Scope of RadicalCC-Coupling by The ldquoTin Methodrdquo Angew Chem Int Ed Engl1984 23 69-70

[59] Giese B Witzel T Synthesis of ldquoC-Disaccharidesrdquo by RadicalC-C Bond Formation Angew Chem Int Ed Engl 1986 25 450-451

[60] Witczak Z J Chhabra R Chojnacki J C-Disaccharides IStereoselective Approach to β-(1rarr4)-3-Deoxy-C-Disaccharidesfrom Levoglucosenone Carb Res 1997 301 167-175

[61] Vogel P Synthesis of Rare Carbohydrates and Analogues Startingfrom Enantiomerically Pure 7-Oxabicyclo[221]heptyl Derivatives(ldquoNaked Sugarsrdquo) Current Org Chem 2000 4 455-480

[62] Viodeacute C Vogel P Synthesis of The C-Disaccharide α-C(1rarr3)-L-Fucopyranoside of N-Acetylgalactosamine J Carb Chem2001 20 733-746

[63] Xin Y C Mallet J M Sinayuml P An Expeditious Synthesis of AC-Disaccharide Using A Temporary Silaketal Connection J ChemSoc Chem Commun 1993 864-865

[64] (a) Petitou M Herault P Lormeau J-C Helmboldt A MalletJ-M Sinayuml P Herbert J-M Introducing A C-InterglycosidicBond in A Biologically Active Pentasaccharide Hardly Affects ItsBiological Properties Bioorg Med Chem 1998 6 1509-1516 (b)Sinayuml P Advances in The Synthesis of the Carbohydrate MimicsPure Appl Chem 1998 70 1495-1499

[65] Sinayuml P Chemical Synthesis of Oligosaccharide Mimetics PureAppl Chem 1998 70 407-410


[67] Vauzeilles B Sinayuml P Selective Radical Synthesis of β-C-Disaccharides Tetrahedron Lett 2001 42 7269-7272


organization of this review is based on the type of chemistryused to assemble the target C-oligosaccharides The chemistryinvolved includes anionic and cationic chemistry reductivesamariation cyclization methodology and free radicalapproaches Methods that afford the C-oligosaccharides withhigh stereoselectivity at the anomeric center (α or β) areclearly desirable This selectivity can be controlled by eitherstarting with a stereochemically defined C-glycoside whichis then coupled with another sugar or by controlling thestereochemistry of the newly formed center

2 ANIONIC APPROACHES

21 Enolate Anions

Fraser-Reid and Jarosz coupled two monosaccharideunits through a directed aldol reaction [10] Aldehyde 1 wasdeprotonated with (Me3Si)2NLi (LiHMDS) to give thechelated enolate 2 which was condensed with aldehyde 3 togive 4a as the major product (Scheme 1)

The zinc-copper-mediated reaction between 5 and 6 givesrise to the generation of single product 7 in 78 yielddemonstrating a remarkable double stereoselectivity with astrong preference for α-C-glycosylation of the ulosyl bromide

together with the elaboration of the (R) configuration for theCHOH group linking the pyranoid moieties (Scheme 2) [11]

Vogel utilized a ldquonaked sugarrdquo approach for the synthesisof an aza-C-disaccharide Enolate derived from 8 wascoupled with aldehyde 9 to give the adduct 10 in 61 yieldThe ketone was reduced and the resulting diol wasacetylated This was followed by selenoxide elimination toafford olefin 11 which was converted to 12 as shown inScheme 3 [12]

Cross-aldol reaction of racemic aldehyde 14 with enan-tiomerically pure lithium enolate of (-)-(1R4R5R6R)- or (-)-(1S4S5S6S)-13 results in mixtures composed mostly ofenantiomerically pure (+)-15 and (-)-15 respectively in 37-48 (only one of the isomers is shown in Scheme 4) [13]

Vogel and co-workers use a novel approach to C-disaccharide synthesis that involves conjugate addition andenolate trapping [14] Levoglucosenone 16 was treated withMe2AlSPh to give the aluminium enolate 17 Condensationof 17 with aldehyde 18 gave the aldol product that wasreduced with DIBAL to 20 Treatment of 20 with acidicmethanol afforded the (1rarr3)-C-disaccharide 21 (Scheme 5)

Scheme (1)

Scheme (2)

OO

OOBn

CHO

LiHMDS

5R

OO

OOBn

OHC

O

OBn OMe

OBn

OBn

C

OH6R

OO

OBnO

CHOLi

5S

OO

OOBn

OHC

O

OBn OMe

OBn

OBn

C

OH

O

OBn OMe

OBn

OBn

CHO

6S

+

1 2 3

4a 4b

O

O

Br

OBz

BzO

BzO

OO

O

O

O

O

O

O

OBz

BzO

BzO

OH

O

O

O

OO

5

1 Zn-Cu THF -35degC

2 NaHCO3

6

7 78








Scheme (3)

Scheme (4)

NCbz

BnO

O

O

O

Cl

OAc

OAc

NCbzBnO

OO

O

PhSe

Cl O

OH

NCbz

CHO

OBnO

O

HO

N

OBn

OAc

CO2Me

AcO

OMe

CbzOMe

OAc OAc

O

PhSe

Cl OTHF -95 o C



LiHMDS -78 oC

8

9

10

1112

O

BnO

TBSO

O

OBnO

BzO

OBz

Br

CHO

OTIPS

O

BnO

TBSO

O

OBnO

BzO

OBz

Br

OTIPS

OH1 LiHMDS

2

1315

14


Scheme (5)

Scheme (6)

OO

O

Me2AlSPh OAlMe2O

O

SPh

O

OH

O

O

OO

O

OH

SPh

OH

O

HO

HO

OMeOH

OMe

HO

O

O

SPhO

O

O

OO

H

HO

HO

OO

O

SPhO

O

OO

HOH

DIBAL

MeOHTsOH

50 o C

16 17

18

19

2021

OO

bull

OR

O

CHOOMe

OO

NaBH4

OOH

bull

OR

OOMe

OO

OH

OO

bull

OR

OOMe

OO

HO

OO

bull

OR

OOMe

OO

OH

Me2AlSPh -78 degC

R = (t-Bu)Me2Si

22

23

24 15

+

25 2926 77


Scheme (7)

Scheme (8)





OO

OR OR

O SiMePh

O

HO

PhMe2SiZnMe2 Li

O

TBSO

TBSO

OTBS

OTBS

H

O

O

OR

SiMePh

TBSO

OTBS

OTBS

OH

HOHO

TBSO

O

O

TBSO

TBSO

OTBS

OTBS

OH

H

O

OR

SiMePh

Me4NBH(OAc)3

R = (t-Bu)Me2Si

+

1 THF -78 oC

2 NH4Cl H2O

3 HCl H2O 20 oC

1 (c-hex) 2BCl Et3N

2

27

28

29

30 24 over 2 steps31 59

O

O

O

O O

NO2

TBAF

O

OH

OO

OO

O

O

OO O

NO2

OO

O

OO

OH

O

O

OO O

OO

O

OO

H

OAc

32

3334 78


35 89






Scheme (9)

Scheme (10)

OAcO

AcOOAc

OAc

NO2O

OH

O

O

OO

OHO

HOOH

OH

O

HO

HOOH

OH

Bu3 SnH

OAcO

AcOOAc

OAc

NO2

OO

O

OO

OH

OAcO

AcOOAc

OAc

X

OO

O

OO

KF 18-C-6 MeCN


38 X = NO 2

39 X = H 57

1 NaOMe

2 H3O+

36

33

37

40 89 over 2 st eps

CHO

O

O

O

O

CH2OPiv

OAcO

AcOOAc

OAc

NO2

OHO

HOOH

OH

O OH

OH

HO

OH

OAcO

AcOOAc

OAc

NO2

PivO

OH

O

O

O

O

OAcO

AcOOAc

OAc

NO2

PivO

O

O

O

O


1 AcOH

2 Ac2O-BF3 OEt

KF 18-C-6 MeCN

41 36

42

4344

3 Bu3SnH AIBN

4 NaOMe

5 H3O+







Scheme (11)

Scheme (12)

OBnO

OBnOMe

BnO

NO2

OBnO

OBn

BnO

OBn

CHO

OHO

OH

HO

OH

OHO

OHOMe

HO

OBnO

OBn

BnO

OBn

OBnO

OBnOMe

BnO

NO2R

OBnO

OBn

BnO

OBn

OBnO

OBnOMe

BnO

KF 18-C-6 MeCN+

1 n-BuLi2 PTC-Cl

51 R = OH

52 R = OC(S)OPh

Bu3 SnH AIBN

1 TsNHNH NaOAc

2 Na NH3

49

50

5354

OAcO

OAc

AcOO

OAcO

OAc

OAc

NO2OAc

OAc

AcO

OAcO

BnOOBn

OMe

BnO

OO

AcOOAc

OAc

OAcO

OMe

BnO O

BnOOBn

O

OO

AcOOAc

OAc

NO2

OAcO

OAc

AcO

OAcO

BnOOBn

OMe

BnO

OH

KF 18-C-6 MeCN


5 NaOMe MeOH

45

46

47

48





Scheme (13)

Scheme (14)

BnO

OBn

O2N

OMe

O

CHO

OBnO

OBn

BnO

OMe

OHO

OH

OHO

OH

HO

OMe

OBnO

OBn

OBnO

OBn

BnO

HO

NO2

OMe

OBnO

OBn

OBnO

OBn

BnO

X

+

KF 18-C-6 MeCN


58 X = NO 2


Bu3SnH AIBN

Pd(OH)2 H2

rt 1 atm 24 h

40

60 74

55

56

57

O

BnOOBn

BnO

OBn

OH

O

OHNO2

O

O

BnOOBn

BnO

OBn

OH

O

ONO2

O

O

O

O

O

AcOOAc

AcO

OAc

O

OAc OAc

OAc

O

BnOOBn

BnO

OBn

NO2OH

Et3 N MeCN

1Bu3 SnH AIBN

2 BF OEt Et3SH

3 L-SelectrideTHF

64 61 in 3 steps

1 Pd(OH)2 C6 H10

2 Ac2O TESOTF

61 63 43

62

65




Scheme (15)

Scheme (16)

OBnO

BnO

H

OBn

OH

OOBn

BnO

OBn

OBn

BnO

OBn

OBn

OBnO

BnO

OBn

OH

SO2

O

OBn

O O

AcO

AcO

AcO

OAc

OAc

OAc

OAc

OAc

OBnO

BnO

OBn

OH

I

O

HS

OBn

BnO

OBn

OBn

68 90 over 2 steps

KOH CCl4 t-BuOH H2O

1 H2 PdC

2 Ac2O Pyr

70 69 over 2 steps

+

1 K2CO3

2 mCPA66

67

69

O

BnOOBn

BnO

OBn

OH

(EtO)2P(O)CH2CO2Et

OBn

OBn

OBnO

OBn

OBnO

BnOOBn

OBn

X

O OBn

OBn

BnOOBn

OBnO

BnOOBn

OBn

OBnO

BnOOBn

OBn

R

OBnO

BnOOBn

OBn

SH

LiAlH4

OAc

AcOOAc

O OAcOAcOAcO

OAc

OAc

1 H2 Pd(OH)2C

2 Ac2 O Pyr

NaH THF

72 R = CO2Et

73 R = CH2OH

66 over 3 steps

K2CO3 acetone

76 X = S

77 X = SO2 79

Oxone THF MeOH H2 O

KOH CCl4 aq tBuOH

78 57ZE 8812

79

71

75





Scheme (17)

Scheme (18)

O

O O

O

O OH

O OMe

OBnBnO

SO2

P

EtO

EtO

O

OBn

O

OMe

OAc

OAc

OAcO

O O

O

O

O

OO OMe

OBnBnO

SO2

OBn

O

O O

O

O O

O

O

O

OMe

OBn

OBn

OBn

83 50 E only

80

+

NaH THF -78 oC

82 86αβ 11

KOHAl2O3

CBr2F2 CH2Cl2

tBuOH 5 oC

2 h

1 H2PdC EtOAc RT 7h

2 Ac2 O Pyr RT

84 69 over 2 st eps

81

O

O O

O

O OH POEt

OEt

O

SO2

P

EtO

EtOO

O

O

O

OO

O

O

O

O O

O

O

O O

O

O

O

O SO2

O

O

O

O

O

O O

O

OO

O

O

85 75βαββ ca 31

86 66β αββ = 141 E only

H2PdC EtOAc

87 76βαβ β = 141

21 NaH THF -78 o C

80 (2 equiv)











25 C-1 Vinyl Anions


Scheme (19)

OCH3

O O

OPhS

PhS

O O

OO

OCH3

O O

OO O

O H

OCH3

O O

OPhSPhS

O O

O OH

OCH3

O O

OO O

O OH

+

n-BuLi THF -78 oC


Et3SiH BF3 OEt2

90 77


-78 oC

88

89







Scheme (20)

Scheme (21)

OO O

O

O CHO

O

BnOOBn

BnO

OBn

CHO

OBn

CHO

BnO

O

BnOBnO

O

BnOOBn

BnO OBn

CHO

PPh3I-

OO

O

OO

O

OMeOBn

OBn

OBn

PPh3I-

OCHO

O

PPh3I-

ORRO

RO

OO

ORRHO

OO

OR

+ +

+

( 93 - 96 )

( 97 - 98 )

BuLi THF-HMPA

-30 iexclaelig

99

Reduction

100

+

93 9495

96 97 98

O

OBnBnO

BnO

OO

O

OO

HO

O

O

OO

PPh3I-

O

OHHO

HO

O

HOOH OH

HO

OBnBnO

CHO

BnO

O

+

BuLi THF-HMPA

-30 oC

1 p-MeC 6H4SO2-

NH2NH2 AcONa

2 H2 Pd(OH)2 3 bar

3 Amberli te H+

+

10197

102

103





Scheme (22)

O

BnOOBn

BnO OTBDPS

PPh3I-

BnO

H

O

BnOOBn

OTBDPS

OO

O

OO

O

CHOO

O

OO

O

BnO

O

BnOOBn

BnO

OO

O

OO

H

HOBn

BnO OTBDPS

O

BnOOBn

BnO O

OO

O

OO

H

OBn

BnO OTBDPS

PPh3I-

O

BnO

O

BnOOBn

BnO OTBDPS

PPh3I-

O

AcOOAc

AcO

O

AcOOAc

AcO

OO

O

OO

O

AcOOAc

AcO OAc

O

BnOOBn

BnO

O

BnOOBn

BnO

OO

O

OO

H

H

O

BnOOBn

BnO OTBDPS

H

1 TBAF2 PCC

+107 36

+

1 TBAF2 PCC3

+


104

33

105

106104

104

108109

BuLi THF-HMPA

-50 o C

70EZ 19

BuLi THF-HMPA

-50 o C







Scheme (23)

Scheme (24)

BnOO

OBnCHO

OBn

O

OBn

PPh3I-

OBn

OBn

O

OBn

BnOBnO

O

OBnOBn

OBnH

O

OH

HOHO

O

OHOH

OH+

BuLi

THF-HMPA

-20 oC+

1 TBAF2 H2 Pd(OH)2C

112 65 113 100

110

111

O

OBnCHO

OBnBnO

O

OBn

BnOBnO

O

OBnCH(OiPr)2

OBnH

O

OBnCH(OiPr)2

PPh3I-

OBn

O

OBn

BnOBnO

O

OBn

OBnH

O

OBnOBn

BnOH

O

OH

HOHO

O

OH

OH

O

OHOH

HO

++

BuLi

THF-HMPA

-20 oC

BuLi

THF-HMPA

-20 oC

TFA H2 O THF rt

115 49

116 R = CH(OiPr)2

117 R = CHO

118 45

H2 Pd(OH)2C

110

114

114

119


Scheme (25)

Scheme (26)

OBn

R1

R2

PPh3BF4-O

O

OOHC

O

O

O

O

O

O

O

O

HO

O

O

O

O

O O

OBn

R1

R2

O

O

O

O

O

O

H

O

OBn

R1

R2

O

O

O

O

O

O

O

O

OBn

R1

R2

O

O

O

+

BCl3 (005 equiv)

MS 4A CH2 Cl2 0 o C

+



R1 R2 = OBn H

120a - b

121

122a - b

123a - b

124

125a - b

OTBDPS

BnO X

SO Ph

O

BnO

OHCO

BnO

OMeOBn

OBn

O

BnO

OTBDPS

BnO

SO Ph

O

BnO

OMeOBn

OBn

O

HO

OMeOH

OHO

HOHO

OH

OH

128

229 74

1 RaNi (74)

2 BH3 DMS

NaOH H 2O2 (74)

3 H2 PdC (70)

130 74

LDA THF

-100 oC

126 X = H

127 X = Li


Scheme (27)

Scheme (28)










O

BnO

OTBDPS

BnO X

SO Ph

O

BnO

OBn

BnO Li

SO Ph

DMF

OHO

HOOH

OH

O OH

OH

HO

OHOH

O

BnO

OTBDPS

BnO

SO Ph

O

OBn

OBnOBnSO

Ph

OH

131 X = Li

132 X = CHO

THF -100 oC

1 Ra-Ni

2 BH3 DMS NaOH H2O2

3 H2 PdC

131

133

134

OBnO

OBnOMe

BnO

Li

OBnO

BnOOBn

OBn

OOBn

OBnOMeBnO

OH

OBnO

BnOOBn

OBn

O

n-BuLi

BnO

OMe

BnO

BrBr

O

OBn

OHO

OH

OH

HO

OHO

OH

HO

OMe

O

BnO

OMeOBn

O

BnO

139 92

1BF3 OEt2 EtOH

2 H2 PdC AcOH

140 52 over 2 steps

135 136 137

138

CBr4 PPh3








Scheme (29)

O

BnO

BnOOBn

OBn

OOBn

OBnOMe

OBnOH

O

BnO

BnO

OBn

OBn

O

O

BnOOBn

OMe

BnO

Li

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnOBnO

OBn

OBnBnO

O

BnO

BnO

OBn

O

OBnO

OBn

OBnBnO

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OMe



1 BF3 OEt2 Et3 OH

2 H2 PtO2 EtOAc

145 76

1 H2 SO4 AcOH

2 PCC

146 62

repeat steps

repeat st eps

141 142

143

147

148


Scheme (30)

Scheme (31)

O

BnOOBn

OMe

Li

BnO

OPivBnO

OBn

OBn

BnO

O OO

BF3 OEt2

OBnO

OBn

OBn

BnO

OO

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

CAN

OBnO

OBn

OBn

BnO

OO

OO

BnOOBn

BnO

OMe

OHBnO

OBn

OBn

BnO

OHO

O

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

OPivBnO

OBn

OBn

BnO

OH OO

O

OMe

BnOOBn

BnO

OAcO

OAc

OAc

AcO

OAcOAc

OAcO

OAc

AcO

OMe

1

2 NaOMe MeOH


with a-isomer

1 Et3N Pyr H2O

2 H2 PdC H+

3 Ac2 O Pyr

149 151

152153

154 155

150

OBn

BnO

OBnO

OBn

BnO

OBnO

BnO

MeO

OBnO

OBn

BnO

O

OMe

AcO

OAcO

OAc

OAc

AcO

OAcO

OAc

O

BnOOBn

OMe

BnO

159 74 over 2 steps

+

BuLi ZnCl2 THF

1 H2 PdC2 Ac2O Pyr

156 157

158 59


Scheme (32)

Scheme (33)



OBnO

OBn

BnO

O

OBnO

ClZnO

OBn

BnOCl

R

OBnO

O

OBn

BnOCl

ZnR

O

ZnR

OBnO

OBn

BnO

160 161

162163

O

OBn

OBnBnO

O

O

OBn

OBnBnO H

TMS

O

OBn

OBnBnO H

O

OBn

BnO

OBnHO

O

OBn

OBnBnO OH

TMS

OBnBnO HO

OBn

TMS

O

OR

ORRO H

O

OR

RO

OR

OBn

OBnBnO

H

TMS

O+

K2CO3 MeOH

1 n-BuLi THF -78 oC

2 164

164165 66

166α 60 166β 13167 97


168 85

169 R = Bn 83


H2 (1 atm)Pd(OH) 2C

TMS-acetyl ene


-78 o C


O

OHCOBn

OBnBnO

OMe

O

CO2MeAcO

OAcAcHN

OAc

SO2

NAcO

OBnH

H

OBn

OBn

H

O

OMeH HH

A

O

CO2MeAcO

OAcAcHN

OAc

O

OBnOMe

OBnOBn

HO

AcO

+

Nu

174175

176

SmI2 THF

Scheme (34)

Scheme (35)

Scheme (36)

O

BnO

BnO

BnO

Si lylO

O2S N

O

BnO

HO R2R1

BnOBnO

SilylO

OBnO

BnO

BnO

SilylO

Sm(III)

R1COR2 SmI2 THF

171 172

173

NHBoc

OAcO

AcO

AcHN O

O

CO2BnO

OO

OO

OH

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

R2

O

CO2Me

AcHN

OAc

AcO

R1

AcO

AcO

AcHNO CO2Bn

NHBoc

AcO

OAc

O

Zn(BH4)2

180 R1 R2 = H OH ( RS 11)

181 R1 R2 = O

182 R1 = H R2 = OH de gt 90

DMSO Ac2O

177178

179

13 steps

22 equiv SmI2 THF


Scheme (37)

Fig (2)




4 CATIONIC METHODS


OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO


+

Ac2O Pyr

187 X = OMP

188 X = SPh 73



+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3















Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331







































































Scheme (3)

Scheme (4)

NCbz

BnO

O

O

O

Cl

OAc

OAc

NCbzBnO

OO

O

PhSe

Cl O

OH

NCbz

CHO

OBnO

O

HO

N

OBn

OAc

CO2Me

AcO

OMe

CbzOMe

OAc OAc

O

PhSe

Cl OTHF -95 o C



LiHMDS -78 oC

8

9

10

1112

O

BnO

TBSO

O

OBnO

BzO

OBz

Br

CHO

OTIPS

O

BnO

TBSO

O

OBnO

BzO

OBz

Br

OTIPS

OH1 LiHMDS

2

1315

14


Scheme (5)

Scheme (6)

OO

O

Me2AlSPh OAlMe2O

O

SPh

O

OH

O

O

OO

O

OH

SPh

OH

O

HO

HO

OMeOH

OMe

HO

O

O

SPhO

O

O

OO

H

HO

HO

OO

O

SPhO

O

OO

HOH

DIBAL

MeOHTsOH

50 o C

16 17

18

19

2021

OO

bull

OR

O

CHOOMe

OO

NaBH4

OOH

bull

OR

OOMe

OO

OH

OO

bull

OR

OOMe

OO

HO

OO

bull

OR

OOMe

OO

OH

Me2AlSPh -78 degC

R = (t-Bu)Me2Si

22

23

24 15

+

25 2926 77


Scheme (7)

Scheme (8)





OO

OR OR

O SiMePh

O

HO

PhMe2SiZnMe2 Li

O

TBSO

TBSO

OTBS

OTBS

H

O

O

OR

SiMePh

TBSO

OTBS

OTBS

OH

HOHO

TBSO

O

O

TBSO

TBSO

OTBS

OTBS

OH

H

O

OR

SiMePh

Me4NBH(OAc)3

R = (t-Bu)Me2Si

+

1 THF -78 oC

2 NH4Cl H2O

3 HCl H2O 20 oC

1 (c-hex) 2BCl Et3N

2

27

28

29

30 24 over 2 steps31 59

O

O

O

O O

NO2

TBAF

O

OH

OO

OO

O

O

OO O

NO2

OO

O

OO

OH

O

O

OO O

OO

O

OO

H

OAc

32

3334 78


35 89






Scheme (9)

Scheme (10)

OAcO

AcOOAc

OAc

NO2O

OH

O

O

OO

OHO

HOOH

OH

O

HO

HOOH

OH

Bu3 SnH

OAcO

AcOOAc

OAc

NO2

OO

O

OO

OH

OAcO

AcOOAc

OAc

X

OO

O

OO

KF 18-C-6 MeCN


38 X = NO 2

39 X = H 57

1 NaOMe

2 H3O+

36

33

37

40 89 over 2 st eps

CHO

O

O

O

O

CH2OPiv

OAcO

AcOOAc

OAc

NO2

OHO

HOOH

OH

O OH

OH

HO

OH

OAcO

AcOOAc

OAc

NO2

PivO

OH

O

O

O

O

OAcO

AcOOAc

OAc

NO2

PivO

O

O

O

O


1 AcOH

2 Ac2O-BF3 OEt

KF 18-C-6 MeCN

41 36

42

4344

3 Bu3SnH AIBN

4 NaOMe

5 H3O+







Scheme (11)

Scheme (12)

OBnO

OBnOMe

BnO

NO2

OBnO

OBn

BnO

OBn

CHO

OHO

OH

HO

OH

OHO

OHOMe

HO

OBnO

OBn

BnO

OBn

OBnO

OBnOMe

BnO

NO2R

OBnO

OBn

BnO

OBn

OBnO

OBnOMe

BnO

KF 18-C-6 MeCN+

1 n-BuLi2 PTC-Cl

51 R = OH

52 R = OC(S)OPh

Bu3 SnH AIBN

1 TsNHNH NaOAc

2 Na NH3

49

50

5354

OAcO

OAc

AcOO

OAcO

OAc

OAc

NO2OAc

OAc

AcO

OAcO

BnOOBn

OMe

BnO

OO

AcOOAc

OAc

OAcO

OMe

BnO O

BnOOBn

O

OO

AcOOAc

OAc

NO2

OAcO

OAc

AcO

OAcO

BnOOBn

OMe

BnO

OH

KF 18-C-6 MeCN


5 NaOMe MeOH

45

46

47

48





Scheme (13)

Scheme (14)

BnO

OBn

O2N

OMe

O

CHO

OBnO

OBn

BnO

OMe

OHO

OH

OHO

OH

HO

OMe

OBnO

OBn

OBnO

OBn

BnO

HO

NO2

OMe

OBnO

OBn

OBnO

OBn

BnO

X

+

KF 18-C-6 MeCN


58 X = NO 2


Bu3SnH AIBN

Pd(OH)2 H2

rt 1 atm 24 h

40

60 74

55

56

57

O

BnOOBn

BnO

OBn

OH

O

OHNO2

O

O

BnOOBn

BnO

OBn

OH

O

ONO2

O

O

O

O

O

AcOOAc

AcO

OAc

O

OAc OAc

OAc

O

BnOOBn

BnO

OBn

NO2OH

Et3 N MeCN

1Bu3 SnH AIBN

2 BF OEt Et3SH

3 L-SelectrideTHF

64 61 in 3 steps

1 Pd(OH)2 C6 H10

2 Ac2O TESOTF

61 63 43

62

65




Scheme (15)

Scheme (16)

OBnO

BnO

H

OBn

OH

OOBn

BnO

OBn

OBn

BnO

OBn

OBn

OBnO

BnO

OBn

OH

SO2

O

OBn

O O

AcO

AcO

AcO

OAc

OAc

OAc

OAc

OAc

OBnO

BnO

OBn

OH

I

O

HS

OBn

BnO

OBn

OBn

68 90 over 2 steps

KOH CCl4 t-BuOH H2O

1 H2 PdC

2 Ac2O Pyr

70 69 over 2 steps

+

1 K2CO3

2 mCPA66

67

69

O

BnOOBn

BnO

OBn

OH

(EtO)2P(O)CH2CO2Et

OBn

OBn

OBnO

OBn

OBnO

BnOOBn

OBn

X

O OBn

OBn

BnOOBn

OBnO

BnOOBn

OBn

OBnO

BnOOBn

OBn

R

OBnO

BnOOBn

OBn

SH

LiAlH4

OAc

AcOOAc

O OAcOAcOAcO

OAc

OAc

1 H2 Pd(OH)2C

2 Ac2 O Pyr

NaH THF

72 R = CO2Et

73 R = CH2OH

66 over 3 steps

K2CO3 acetone

76 X = S

77 X = SO2 79

Oxone THF MeOH H2 O

KOH CCl4 aq tBuOH

78 57ZE 8812

79

71

75





Scheme (17)

Scheme (18)

O

O O

O

O OH

O OMe

OBnBnO

SO2

P

EtO

EtO

O

OBn

O

OMe

OAc

OAc

OAcO

O O

O

O

O

OO OMe

OBnBnO

SO2

OBn

O

O O

O

O O

O

O

O

OMe

OBn

OBn

OBn

83 50 E only

80

+

NaH THF -78 oC

82 86αβ 11

KOHAl2O3

CBr2F2 CH2Cl2

tBuOH 5 oC

2 h

1 H2PdC EtOAc RT 7h

2 Ac2 O Pyr RT

84 69 over 2 st eps

81

O

O O

O

O OH POEt

OEt

O

SO2

P

EtO

EtOO

O

O

O

OO

O

O

O

O O

O

O

O O

O

O

O

O SO2

O

O

O

O

O

O O

O

OO

O

O

85 75βαββ ca 31

86 66β αββ = 141 E only

H2PdC EtOAc

87 76βαβ β = 141

21 NaH THF -78 o C

80 (2 equiv)











25 C-1 Vinyl Anions


Scheme (19)

OCH3

O O

OPhS

PhS

O O

OO

OCH3

O O

OO O

O H

OCH3

O O

OPhSPhS

O O

O OH

OCH3

O O

OO O

O OH

+

n-BuLi THF -78 oC


Et3SiH BF3 OEt2

90 77


-78 oC

88

89







Scheme (20)

Scheme (21)

OO O

O

O CHO

O

BnOOBn

BnO

OBn

CHO

OBn

CHO

BnO

O

BnOBnO

O

BnOOBn

BnO OBn

CHO

PPh3I-

OO

O

OO

O

OMeOBn

OBn

OBn

PPh3I-

OCHO

O

PPh3I-

ORRO

RO

OO

ORRHO

OO

OR

+ +

+

( 93 - 96 )

( 97 - 98 )

BuLi THF-HMPA

-30 iexclaelig

99

Reduction

100

+

93 9495

96 97 98

O

OBnBnO

BnO

OO

O

OO

HO

O

O

OO

PPh3I-

O

OHHO

HO

O

HOOH OH

HO

OBnBnO

CHO

BnO

O

+

BuLi THF-HMPA

-30 oC

1 p-MeC 6H4SO2-

NH2NH2 AcONa

2 H2 Pd(OH)2 3 bar

3 Amberli te H+

+

10197

102

103





Scheme (22)

O

BnOOBn

BnO OTBDPS

PPh3I-

BnO

H

O

BnOOBn

OTBDPS

OO

O

OO

O

CHOO

O

OO

O

BnO

O

BnOOBn

BnO

OO

O

OO

H

HOBn

BnO OTBDPS

O

BnOOBn

BnO O

OO

O

OO

H

OBn

BnO OTBDPS

PPh3I-

O

BnO

O

BnOOBn

BnO OTBDPS

PPh3I-

O

AcOOAc

AcO

O

AcOOAc

AcO

OO

O

OO

O

AcOOAc

AcO OAc

O

BnOOBn

BnO

O

BnOOBn

BnO

OO

O

OO

H

H

O

BnOOBn

BnO OTBDPS

H

1 TBAF2 PCC

+107 36

+

1 TBAF2 PCC3

+


104

33

105

106104

104

108109

BuLi THF-HMPA

-50 o C

70EZ 19

BuLi THF-HMPA

-50 o C







Scheme (23)

Scheme (24)

BnOO

OBnCHO

OBn

O

OBn

PPh3I-

OBn

OBn

O

OBn

BnOBnO

O

OBnOBn

OBnH

O

OH

HOHO

O

OHOH

OH+

BuLi

THF-HMPA

-20 oC+

1 TBAF2 H2 Pd(OH)2C

112 65 113 100

110

111

O

OBnCHO

OBnBnO

O

OBn

BnOBnO

O

OBnCH(OiPr)2

OBnH

O

OBnCH(OiPr)2

PPh3I-

OBn

O

OBn

BnOBnO

O

OBn

OBnH

O

OBnOBn

BnOH

O

OH

HOHO

O

OH

OH

O

OHOH

HO

++

BuLi

THF-HMPA

-20 oC

BuLi

THF-HMPA

-20 oC

TFA H2 O THF rt

115 49

116 R = CH(OiPr)2

117 R = CHO

118 45

H2 Pd(OH)2C

110

114

114

119


Scheme (25)

Scheme (26)

OBn

R1

R2

PPh3BF4-O

O

OOHC

O

O

O

O

O

O

O

O

HO

O

O

O

O

O O

OBn

R1

R2

O

O

O

O

O

O

H

O

OBn

R1

R2

O

O

O

O

O

O

O

O

OBn

R1

R2

O

O

O

+

BCl3 (005 equiv)

MS 4A CH2 Cl2 0 o C

+



R1 R2 = OBn H

120a - b

121

122a - b

123a - b

124

125a - b

OTBDPS

BnO X

SO Ph

O

BnO

OHCO

BnO

OMeOBn

OBn

O

BnO

OTBDPS

BnO

SO Ph

O

BnO

OMeOBn

OBn

O

HO

OMeOH

OHO

HOHO

OH

OH

128

229 74

1 RaNi (74)

2 BH3 DMS

NaOH H 2O2 (74)

3 H2 PdC (70)

130 74

LDA THF

-100 oC

126 X = H

127 X = Li


Scheme (27)

Scheme (28)










O

BnO

OTBDPS

BnO X

SO Ph

O

BnO

OBn

BnO Li

SO Ph

DMF

OHO

HOOH

OH

O OH

OH

HO

OHOH

O

BnO

OTBDPS

BnO

SO Ph

O

OBn

OBnOBnSO

Ph

OH

131 X = Li

132 X = CHO

THF -100 oC

1 Ra-Ni

2 BH3 DMS NaOH H2O2

3 H2 PdC

131

133

134

OBnO

OBnOMe

BnO

Li

OBnO

BnOOBn

OBn

OOBn

OBnOMeBnO

OH

OBnO

BnOOBn

OBn

O

n-BuLi

BnO

OMe

BnO

BrBr

O

OBn

OHO

OH

OH

HO

OHO

OH

HO

OMe

O

BnO

OMeOBn

O

BnO

139 92

1BF3 OEt2 EtOH

2 H2 PdC AcOH

140 52 over 2 steps

135 136 137

138

CBr4 PPh3








Scheme (29)

O

BnO

BnOOBn

OBn

OOBn

OBnOMe

OBnOH

O

BnO

BnO

OBn

OBn

O

O

BnOOBn

OMe

BnO

Li

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnOBnO

OBn

OBnBnO

O

BnO

BnO

OBn

O

OBnO

OBn

OBnBnO

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OMe



1 BF3 OEt2 Et3 OH

2 H2 PtO2 EtOAc

145 76

1 H2 SO4 AcOH

2 PCC

146 62

repeat steps

repeat st eps

141 142

143

147

148


Scheme (30)

Scheme (31)

O

BnOOBn

OMe

Li

BnO

OPivBnO

OBn

OBn

BnO

O OO

BF3 OEt2

OBnO

OBn

OBn

BnO

OO

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

CAN

OBnO

OBn

OBn

BnO

OO

OO

BnOOBn

BnO

OMe

OHBnO

OBn

OBn

BnO

OHO

O

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

OPivBnO

OBn

OBn

BnO

OH OO

O

OMe

BnOOBn

BnO

OAcO

OAc

OAc

AcO

OAcOAc

OAcO

OAc

AcO

OMe

1

2 NaOMe MeOH


with a-isomer

1 Et3N Pyr H2O

2 H2 PdC H+

3 Ac2 O Pyr

149 151

152153

154 155

150

OBn

BnO

OBnO

OBn

BnO

OBnO

BnO

MeO

OBnO

OBn

BnO

O

OMe

AcO

OAcO

OAc

OAc

AcO

OAcO

OAc

O

BnOOBn

OMe

BnO

159 74 over 2 steps

+

BuLi ZnCl2 THF

1 H2 PdC2 Ac2O Pyr

156 157

158 59


Scheme (32)

Scheme (33)



OBnO

OBn

BnO

O

OBnO

ClZnO

OBn

BnOCl

R

OBnO

O

OBn

BnOCl

ZnR

O

ZnR

OBnO

OBn

BnO

160 161

162163

O

OBn

OBnBnO

O

O

OBn

OBnBnO H

TMS

O

OBn

OBnBnO H

O

OBn

BnO

OBnHO

O

OBn

OBnBnO OH

TMS

OBnBnO HO

OBn

TMS

O

OR

ORRO H

O

OR

RO

OR

OBn

OBnBnO

H

TMS

O+

K2CO3 MeOH

1 n-BuLi THF -78 oC

2 164

164165 66

166α 60 166β 13167 97


168 85

169 R = Bn 83


H2 (1 atm)Pd(OH) 2C

TMS-acetyl ene


-78 o C


O

OHCOBn

OBnBnO

OMe

O

CO2MeAcO

OAcAcHN

OAc

SO2

NAcO

OBnH

H

OBn

OBn

H

O

OMeH HH

A

O

CO2MeAcO

OAcAcHN

OAc

O

OBnOMe

OBnOBn

HO

AcO

+

Nu

174175

176

SmI2 THF

Scheme (34)

Scheme (35)

Scheme (36)

O

BnO

BnO

BnO

Si lylO

O2S N

O

BnO

HO R2R1

BnOBnO

SilylO

OBnO

BnO

BnO

SilylO

Sm(III)

R1COR2 SmI2 THF

171 172

173

NHBoc

OAcO

AcO

AcHN O

O

CO2BnO

OO

OO

OH

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

R2

O

CO2Me

AcHN

OAc

AcO

R1

AcO

AcO

AcHNO CO2Bn

NHBoc

AcO

OAc

O

Zn(BH4)2

180 R1 R2 = H OH ( RS 11)

181 R1 R2 = O

182 R1 = H R2 = OH de gt 90

DMSO Ac2O

177178

179

13 steps

22 equiv SmI2 THF


Scheme (37)

Fig (2)




4 CATIONIC METHODS


OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO


+

Ac2O Pyr

187 X = OMP

188 X = SPh 73



+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3















Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331

































































Scheme (5)

Scheme (6)

OO

O

Me2AlSPh OAlMe2O

O

SPh

O

OH

O

O

OO

O

OH

SPh

OH

O

HO

HO

OMeOH

OMe

HO

O

O

SPhO

O

O

OO

H

HO

HO

OO

O

SPhO

O

OO

HOH

DIBAL

MeOHTsOH

50 o C

16 17

18

19

2021

OO

bull

OR

O

CHOOMe

OO

NaBH4

OOH

bull

OR

OOMe

OO

OH

OO

bull

OR

OOMe

OO

HO

OO

bull

OR

OOMe

OO

OH

Me2AlSPh -78 degC

R = (t-Bu)Me2Si

22

23

24 15

+

25 2926 77


Scheme (7)

Scheme (8)





OO

OR OR

O SiMePh

O

HO

PhMe2SiZnMe2 Li

O

TBSO

TBSO

OTBS

OTBS

H

O

O

OR

SiMePh

TBSO

OTBS

OTBS

OH

HOHO

TBSO

O

O

TBSO

TBSO

OTBS

OTBS

OH

H

O

OR

SiMePh

Me4NBH(OAc)3

R = (t-Bu)Me2Si

+

1 THF -78 oC

2 NH4Cl H2O

3 HCl H2O 20 oC

1 (c-hex) 2BCl Et3N

2

27

28

29

30 24 over 2 steps31 59

O

O

O

O O

NO2

TBAF

O

OH

OO

OO

O

O

OO O

NO2

OO

O

OO

OH

O

O

OO O

OO

O

OO

H

OAc

32

3334 78


35 89






Scheme (9)

Scheme (10)

OAcO

AcOOAc

OAc

NO2O

OH

O

O

OO

OHO

HOOH

OH

O

HO

HOOH

OH

Bu3 SnH

OAcO

AcOOAc

OAc

NO2

OO

O

OO

OH

OAcO

AcOOAc

OAc

X

OO

O

OO

KF 18-C-6 MeCN


38 X = NO 2

39 X = H 57

1 NaOMe

2 H3O+

36

33

37

40 89 over 2 st eps

CHO

O

O

O

O

CH2OPiv

OAcO

AcOOAc

OAc

NO2

OHO

HOOH

OH

O OH

OH

HO

OH

OAcO

AcOOAc

OAc

NO2

PivO

OH

O

O

O

O

OAcO

AcOOAc

OAc

NO2

PivO

O

O

O

O


1 AcOH

2 Ac2O-BF3 OEt

KF 18-C-6 MeCN

41 36

42

4344

3 Bu3SnH AIBN

4 NaOMe

5 H3O+







Scheme (11)

Scheme (12)

OBnO

OBnOMe

BnO

NO2

OBnO

OBn

BnO

OBn

CHO

OHO

OH

HO

OH

OHO

OHOMe

HO

OBnO

OBn

BnO

OBn

OBnO

OBnOMe

BnO

NO2R

OBnO

OBn

BnO

OBn

OBnO

OBnOMe

BnO

KF 18-C-6 MeCN+

1 n-BuLi2 PTC-Cl

51 R = OH

52 R = OC(S)OPh

Bu3 SnH AIBN

1 TsNHNH NaOAc

2 Na NH3

49

50

5354

OAcO

OAc

AcOO

OAcO

OAc

OAc

NO2OAc

OAc

AcO

OAcO

BnOOBn

OMe

BnO

OO

AcOOAc

OAc

OAcO

OMe

BnO O

BnOOBn

O

OO

AcOOAc

OAc

NO2

OAcO

OAc

AcO

OAcO

BnOOBn

OMe

BnO

OH

KF 18-C-6 MeCN


5 NaOMe MeOH

45

46

47

48





Scheme (13)

Scheme (14)

BnO

OBn

O2N

OMe

O

CHO

OBnO

OBn

BnO

OMe

OHO

OH

OHO

OH

HO

OMe

OBnO

OBn

OBnO

OBn

BnO

HO

NO2

OMe

OBnO

OBn

OBnO

OBn

BnO

X

+

KF 18-C-6 MeCN


58 X = NO 2


Bu3SnH AIBN

Pd(OH)2 H2

rt 1 atm 24 h

40

60 74

55

56

57

O

BnOOBn

BnO

OBn

OH

O

OHNO2

O

O

BnOOBn

BnO

OBn

OH

O

ONO2

O

O

O

O

O

AcOOAc

AcO

OAc

O

OAc OAc

OAc

O

BnOOBn

BnO

OBn

NO2OH

Et3 N MeCN

1Bu3 SnH AIBN

2 BF OEt Et3SH

3 L-SelectrideTHF

64 61 in 3 steps

1 Pd(OH)2 C6 H10

2 Ac2O TESOTF

61 63 43

62

65




Scheme (15)

Scheme (16)

OBnO

BnO

H

OBn

OH

OOBn

BnO

OBn

OBn

BnO

OBn

OBn

OBnO

BnO

OBn

OH

SO2

O

OBn

O O

AcO

AcO

AcO

OAc

OAc

OAc

OAc

OAc

OBnO

BnO

OBn

OH

I

O

HS

OBn

BnO

OBn

OBn

68 90 over 2 steps

KOH CCl4 t-BuOH H2O

1 H2 PdC

2 Ac2O Pyr

70 69 over 2 steps

+

1 K2CO3

2 mCPA66

67

69

O

BnOOBn

BnO

OBn

OH

(EtO)2P(O)CH2CO2Et

OBn

OBn

OBnO

OBn

OBnO

BnOOBn

OBn

X

O OBn

OBn

BnOOBn

OBnO

BnOOBn

OBn

OBnO

BnOOBn

OBn

R

OBnO

BnOOBn

OBn

SH

LiAlH4

OAc

AcOOAc

O OAcOAcOAcO

OAc

OAc

1 H2 Pd(OH)2C

2 Ac2 O Pyr

NaH THF

72 R = CO2Et

73 R = CH2OH

66 over 3 steps

K2CO3 acetone

76 X = S

77 X = SO2 79

Oxone THF MeOH H2 O

KOH CCl4 aq tBuOH

78 57ZE 8812

79

71

75





Scheme (17)

Scheme (18)

O

O O

O

O OH

O OMe

OBnBnO

SO2

P

EtO

EtO

O

OBn

O

OMe

OAc

OAc

OAcO

O O

O

O

O

OO OMe

OBnBnO

SO2

OBn

O

O O

O

O O

O

O

O

OMe

OBn

OBn

OBn

83 50 E only

80

+

NaH THF -78 oC

82 86αβ 11

KOHAl2O3

CBr2F2 CH2Cl2

tBuOH 5 oC

2 h

1 H2PdC EtOAc RT 7h

2 Ac2 O Pyr RT

84 69 over 2 st eps

81

O

O O

O

O OH POEt

OEt

O

SO2

P

EtO

EtOO

O

O

O

OO

O

O

O

O O

O

O

O O

O

O

O

O SO2

O

O

O

O

O

O O

O

OO

O

O

85 75βαββ ca 31

86 66β αββ = 141 E only

H2PdC EtOAc

87 76βαβ β = 141

21 NaH THF -78 o C

80 (2 equiv)











25 C-1 Vinyl Anions


Scheme (19)

OCH3

O O

OPhS

PhS

O O

OO

OCH3

O O

OO O

O H

OCH3

O O

OPhSPhS

O O

O OH

OCH3

O O

OO O

O OH

+

n-BuLi THF -78 oC


Et3SiH BF3 OEt2

90 77


-78 oC

88

89







Scheme (20)

Scheme (21)

OO O

O

O CHO

O

BnOOBn

BnO

OBn

CHO

OBn

CHO

BnO

O

BnOBnO

O

BnOOBn

BnO OBn

CHO

PPh3I-

OO

O

OO

O

OMeOBn

OBn

OBn

PPh3I-

OCHO

O

PPh3I-

ORRO

RO

OO

ORRHO

OO

OR

+ +

+

( 93 - 96 )

( 97 - 98 )

BuLi THF-HMPA

-30 iexclaelig

99

Reduction

100

+

93 9495

96 97 98

O

OBnBnO

BnO

OO

O

OO

HO

O

O

OO

PPh3I-

O

OHHO

HO

O

HOOH OH

HO

OBnBnO

CHO

BnO

O

+

BuLi THF-HMPA

-30 oC

1 p-MeC 6H4SO2-

NH2NH2 AcONa

2 H2 Pd(OH)2 3 bar

3 Amberli te H+

+

10197

102

103





Scheme (22)

O

BnOOBn

BnO OTBDPS

PPh3I-

BnO

H

O

BnOOBn

OTBDPS

OO

O

OO

O

CHOO

O

OO

O

BnO

O

BnOOBn

BnO

OO

O

OO

H

HOBn

BnO OTBDPS

O

BnOOBn

BnO O

OO

O

OO

H

OBn

BnO OTBDPS

PPh3I-

O

BnO

O

BnOOBn

BnO OTBDPS

PPh3I-

O

AcOOAc

AcO

O

AcOOAc

AcO

OO

O

OO

O

AcOOAc

AcO OAc

O

BnOOBn

BnO

O

BnOOBn

BnO

OO

O

OO

H

H

O

BnOOBn

BnO OTBDPS

H

1 TBAF2 PCC

+107 36

+

1 TBAF2 PCC3

+


104

33

105

106104

104

108109

BuLi THF-HMPA

-50 o C

70EZ 19

BuLi THF-HMPA

-50 o C







Scheme (23)

Scheme (24)

BnOO

OBnCHO

OBn

O

OBn

PPh3I-

OBn

OBn

O

OBn

BnOBnO

O

OBnOBn

OBnH

O

OH

HOHO

O

OHOH

OH+

BuLi

THF-HMPA

-20 oC+

1 TBAF2 H2 Pd(OH)2C

112 65 113 100

110

111

O

OBnCHO

OBnBnO

O

OBn

BnOBnO

O

OBnCH(OiPr)2

OBnH

O

OBnCH(OiPr)2

PPh3I-

OBn

O

OBn

BnOBnO

O

OBn

OBnH

O

OBnOBn

BnOH

O

OH

HOHO

O

OH

OH

O

OHOH

HO

++

BuLi

THF-HMPA

-20 oC

BuLi

THF-HMPA

-20 oC

TFA H2 O THF rt

115 49

116 R = CH(OiPr)2

117 R = CHO

118 45

H2 Pd(OH)2C

110

114

114

119


Scheme (25)

Scheme (26)

OBn

R1

R2

PPh3BF4-O

O

OOHC

O

O

O

O

O

O

O

O

HO

O

O

O

O

O O

OBn

R1

R2

O

O

O

O

O

O

H

O

OBn

R1

R2

O

O

O

O

O

O

O

O

OBn

R1

R2

O

O

O

+

BCl3 (005 equiv)

MS 4A CH2 Cl2 0 o C

+



R1 R2 = OBn H

120a - b

121

122a - b

123a - b

124

125a - b

OTBDPS

BnO X

SO Ph

O

BnO

OHCO

BnO

OMeOBn

OBn

O

BnO

OTBDPS

BnO

SO Ph

O

BnO

OMeOBn

OBn

O

HO

OMeOH

OHO

HOHO

OH

OH

128

229 74

1 RaNi (74)

2 BH3 DMS

NaOH H 2O2 (74)

3 H2 PdC (70)

130 74

LDA THF

-100 oC

126 X = H

127 X = Li


Scheme (27)

Scheme (28)










O

BnO

OTBDPS

BnO X

SO Ph

O

BnO

OBn

BnO Li

SO Ph

DMF

OHO

HOOH

OH

O OH

OH

HO

OHOH

O

BnO

OTBDPS

BnO

SO Ph

O

OBn

OBnOBnSO

Ph

OH

131 X = Li

132 X = CHO

THF -100 oC

1 Ra-Ni

2 BH3 DMS NaOH H2O2

3 H2 PdC

131

133

134

OBnO

OBnOMe

BnO

Li

OBnO

BnOOBn

OBn

OOBn

OBnOMeBnO

OH

OBnO

BnOOBn

OBn

O

n-BuLi

BnO

OMe

BnO

BrBr

O

OBn

OHO

OH

OH

HO

OHO

OH

HO

OMe

O

BnO

OMeOBn

O

BnO

139 92

1BF3 OEt2 EtOH

2 H2 PdC AcOH

140 52 over 2 steps

135 136 137

138

CBr4 PPh3








Scheme (29)

O

BnO

BnOOBn

OBn

OOBn

OBnOMe

OBnOH

O

BnO

BnO

OBn

OBn

O

O

BnOOBn

OMe

BnO

Li

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnOBnO

OBn

OBnBnO

O

BnO

BnO

OBn

O

OBnO

OBn

OBnBnO

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OMe



1 BF3 OEt2 Et3 OH

2 H2 PtO2 EtOAc

145 76

1 H2 SO4 AcOH

2 PCC

146 62

repeat steps

repeat st eps

141 142

143

147

148


Scheme (30)

Scheme (31)

O

BnOOBn

OMe

Li

BnO

OPivBnO

OBn

OBn

BnO

O OO

BF3 OEt2

OBnO

OBn

OBn

BnO

OO

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

CAN

OBnO

OBn

OBn

BnO

OO

OO

BnOOBn

BnO

OMe

OHBnO

OBn

OBn

BnO

OHO

O

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

OPivBnO

OBn

OBn

BnO

OH OO

O

OMe

BnOOBn

BnO

OAcO

OAc

OAc

AcO

OAcOAc

OAcO

OAc

AcO

OMe

1

2 NaOMe MeOH


with a-isomer

1 Et3N Pyr H2O

2 H2 PdC H+

3 Ac2 O Pyr

149 151

152153

154 155

150

OBn

BnO

OBnO

OBn

BnO

OBnO

BnO

MeO

OBnO

OBn

BnO

O

OMe

AcO

OAcO

OAc

OAc

AcO

OAcO

OAc

O

BnOOBn

OMe

BnO

159 74 over 2 steps

+

BuLi ZnCl2 THF

1 H2 PdC2 Ac2O Pyr

156 157

158 59


Scheme (32)

Scheme (33)



OBnO

OBn

BnO

O

OBnO

ClZnO

OBn

BnOCl

R

OBnO

O

OBn

BnOCl

ZnR

O

ZnR

OBnO

OBn

BnO

160 161

162163

O

OBn

OBnBnO

O

O

OBn

OBnBnO H

TMS

O

OBn

OBnBnO H

O

OBn

BnO

OBnHO

O

OBn

OBnBnO OH

TMS

OBnBnO HO

OBn

TMS

O

OR

ORRO H

O

OR

RO

OR

OBn

OBnBnO

H

TMS

O+

K2CO3 MeOH

1 n-BuLi THF -78 oC

2 164

164165 66

166α 60 166β 13167 97


168 85

169 R = Bn 83


H2 (1 atm)Pd(OH) 2C

TMS-acetyl ene


-78 o C


O

OHCOBn

OBnBnO

OMe

O

CO2MeAcO

OAcAcHN

OAc

SO2

NAcO

OBnH

H

OBn

OBn

H

O

OMeH HH

A

O

CO2MeAcO

OAcAcHN

OAc

O

OBnOMe

OBnOBn

HO

AcO

+

Nu

174175

176

SmI2 THF

Scheme (34)

Scheme (35)

Scheme (36)

O

BnO

BnO

BnO

Si lylO

O2S N

O

BnO

HO R2R1

BnOBnO

SilylO

OBnO

BnO

BnO

SilylO

Sm(III)

R1COR2 SmI2 THF

171 172

173

NHBoc

OAcO

AcO

AcHN O

O

CO2BnO

OO

OO

OH

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

R2

O

CO2Me

AcHN

OAc

AcO

R1

AcO

AcO

AcHNO CO2Bn

NHBoc

AcO

OAc

O

Zn(BH4)2

180 R1 R2 = H OH ( RS 11)

181 R1 R2 = O

182 R1 = H R2 = OH de gt 90

DMSO Ac2O

177178

179

13 steps

22 equiv SmI2 THF


Scheme (37)

Fig (2)




4 CATIONIC METHODS


OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO


+

Ac2O Pyr

187 X = OMP

188 X = SPh 73



+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3















Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331

































































Scheme (7)

Scheme (8)





OO

OR OR

O SiMePh

O

HO

PhMe2SiZnMe2 Li

O

TBSO

TBSO

OTBS

OTBS

H

O

O

OR

SiMePh

TBSO

OTBS

OTBS

OH

HOHO

TBSO

O

O

TBSO

TBSO

OTBS

OTBS

OH

H

O

OR

SiMePh

Me4NBH(OAc)3

R = (t-Bu)Me2Si

+

1 THF -78 oC

2 NH4Cl H2O

3 HCl H2O 20 oC

1 (c-hex) 2BCl Et3N

2

27

28

29

30 24 over 2 steps31 59

O

O

O

O O

NO2

TBAF

O

OH

OO

OO

O

O

OO O

NO2

OO

O

OO

OH

O

O

OO O

OO

O

OO

H

OAc

32

3334 78


35 89






Scheme (9)

Scheme (10)

OAcO

AcOOAc

OAc

NO2O

OH

O

O

OO

OHO

HOOH

OH

O

HO

HOOH

OH

Bu3 SnH

OAcO

AcOOAc

OAc

NO2

OO

O

OO

OH

OAcO

AcOOAc

OAc

X

OO

O

OO

KF 18-C-6 MeCN


38 X = NO 2

39 X = H 57

1 NaOMe

2 H3O+

36

33

37

40 89 over 2 st eps

CHO

O

O

O

O

CH2OPiv

OAcO

AcOOAc

OAc

NO2

OHO

HOOH

OH

O OH

OH

HO

OH

OAcO

AcOOAc

OAc

NO2

PivO

OH

O

O

O

O

OAcO

AcOOAc

OAc

NO2

PivO

O

O

O

O


1 AcOH

2 Ac2O-BF3 OEt

KF 18-C-6 MeCN

41 36

42

4344

3 Bu3SnH AIBN

4 NaOMe

5 H3O+







Scheme (11)

Scheme (12)

OBnO

OBnOMe

BnO

NO2

OBnO

OBn

BnO

OBn

CHO

OHO

OH

HO

OH

OHO

OHOMe

HO

OBnO

OBn

BnO

OBn

OBnO

OBnOMe

BnO

NO2R

OBnO

OBn

BnO

OBn

OBnO

OBnOMe

BnO

KF 18-C-6 MeCN+

1 n-BuLi2 PTC-Cl

51 R = OH

52 R = OC(S)OPh

Bu3 SnH AIBN

1 TsNHNH NaOAc

2 Na NH3

49

50

5354

OAcO

OAc

AcOO

OAcO

OAc

OAc

NO2OAc

OAc

AcO

OAcO

BnOOBn

OMe

BnO

OO

AcOOAc

OAc

OAcO

OMe

BnO O

BnOOBn

O

OO

AcOOAc

OAc

NO2

OAcO

OAc

AcO

OAcO

BnOOBn

OMe

BnO

OH

KF 18-C-6 MeCN


5 NaOMe MeOH

45

46

47

48





Scheme (13)

Scheme (14)

BnO

OBn

O2N

OMe

O

CHO

OBnO

OBn

BnO

OMe

OHO

OH

OHO

OH

HO

OMe

OBnO

OBn

OBnO

OBn

BnO

HO

NO2

OMe

OBnO

OBn

OBnO

OBn

BnO

X

+

KF 18-C-6 MeCN


58 X = NO 2


Bu3SnH AIBN

Pd(OH)2 H2

rt 1 atm 24 h

40

60 74

55

56

57

O

BnOOBn

BnO

OBn

OH

O

OHNO2

O

O

BnOOBn

BnO

OBn

OH

O

ONO2

O

O

O

O

O

AcOOAc

AcO

OAc

O

OAc OAc

OAc

O

BnOOBn

BnO

OBn

NO2OH

Et3 N MeCN

1Bu3 SnH AIBN

2 BF OEt Et3SH

3 L-SelectrideTHF

64 61 in 3 steps

1 Pd(OH)2 C6 H10

2 Ac2O TESOTF

61 63 43

62

65




Scheme (15)

Scheme (16)

OBnO

BnO

H

OBn

OH

OOBn

BnO

OBn

OBn

BnO

OBn

OBn

OBnO

BnO

OBn

OH

SO2

O

OBn

O O

AcO

AcO

AcO

OAc

OAc

OAc

OAc

OAc

OBnO

BnO

OBn

OH

I

O

HS

OBn

BnO

OBn

OBn

68 90 over 2 steps

KOH CCl4 t-BuOH H2O

1 H2 PdC

2 Ac2O Pyr

70 69 over 2 steps

+

1 K2CO3

2 mCPA66

67

69

O

BnOOBn

BnO

OBn

OH

(EtO)2P(O)CH2CO2Et

OBn

OBn

OBnO

OBn

OBnO

BnOOBn

OBn

X

O OBn

OBn

BnOOBn

OBnO

BnOOBn

OBn

OBnO

BnOOBn

OBn

R

OBnO

BnOOBn

OBn

SH

LiAlH4

OAc

AcOOAc

O OAcOAcOAcO

OAc

OAc

1 H2 Pd(OH)2C

2 Ac2 O Pyr

NaH THF

72 R = CO2Et

73 R = CH2OH

66 over 3 steps

K2CO3 acetone

76 X = S

77 X = SO2 79

Oxone THF MeOH H2 O

KOH CCl4 aq tBuOH

78 57ZE 8812

79

71

75





Scheme (17)

Scheme (18)

O

O O

O

O OH

O OMe

OBnBnO

SO2

P

EtO

EtO

O

OBn

O

OMe

OAc

OAc

OAcO

O O

O

O

O

OO OMe

OBnBnO

SO2

OBn

O

O O

O

O O

O

O

O

OMe

OBn

OBn

OBn

83 50 E only

80

+

NaH THF -78 oC

82 86αβ 11

KOHAl2O3

CBr2F2 CH2Cl2

tBuOH 5 oC

2 h

1 H2PdC EtOAc RT 7h

2 Ac2 O Pyr RT

84 69 over 2 st eps

81

O

O O

O

O OH POEt

OEt

O

SO2

P

EtO

EtOO

O

O

O

OO

O

O

O

O O

O

O

O O

O

O

O

O SO2

O

O

O

O

O

O O

O

OO

O

O

85 75βαββ ca 31

86 66β αββ = 141 E only

H2PdC EtOAc

87 76βαβ β = 141

21 NaH THF -78 o C

80 (2 equiv)











25 C-1 Vinyl Anions


Scheme (19)

OCH3

O O

OPhS

PhS

O O

OO

OCH3

O O

OO O

O H

OCH3

O O

OPhSPhS

O O

O OH

OCH3

O O

OO O

O OH

+

n-BuLi THF -78 oC


Et3SiH BF3 OEt2

90 77


-78 oC

88

89







Scheme (20)

Scheme (21)

OO O

O

O CHO

O

BnOOBn

BnO

OBn

CHO

OBn

CHO

BnO

O

BnOBnO

O

BnOOBn

BnO OBn

CHO

PPh3I-

OO

O

OO

O

OMeOBn

OBn

OBn

PPh3I-

OCHO

O

PPh3I-

ORRO

RO

OO

ORRHO

OO

OR

+ +

+

( 93 - 96 )

( 97 - 98 )

BuLi THF-HMPA

-30 iexclaelig

99

Reduction

100

+

93 9495

96 97 98

O

OBnBnO

BnO

OO

O

OO

HO

O

O

OO

PPh3I-

O

OHHO

HO

O

HOOH OH

HO

OBnBnO

CHO

BnO

O

+

BuLi THF-HMPA

-30 oC

1 p-MeC 6H4SO2-

NH2NH2 AcONa

2 H2 Pd(OH)2 3 bar

3 Amberli te H+

+

10197

102

103





Scheme (22)

O

BnOOBn

BnO OTBDPS

PPh3I-

BnO

H

O

BnOOBn

OTBDPS

OO

O

OO

O

CHOO

O

OO

O

BnO

O

BnOOBn

BnO

OO

O

OO

H

HOBn

BnO OTBDPS

O

BnOOBn

BnO O

OO

O

OO

H

OBn

BnO OTBDPS

PPh3I-

O

BnO

O

BnOOBn

BnO OTBDPS

PPh3I-

O

AcOOAc

AcO

O

AcOOAc

AcO

OO

O

OO

O

AcOOAc

AcO OAc

O

BnOOBn

BnO

O

BnOOBn

BnO

OO

O

OO

H

H

O

BnOOBn

BnO OTBDPS

H

1 TBAF2 PCC

+107 36

+

1 TBAF2 PCC3

+


104

33

105

106104

104

108109

BuLi THF-HMPA

-50 o C

70EZ 19

BuLi THF-HMPA

-50 o C







Scheme (23)

Scheme (24)

BnOO

OBnCHO

OBn

O

OBn

PPh3I-

OBn

OBn

O

OBn

BnOBnO

O

OBnOBn

OBnH

O

OH

HOHO

O

OHOH

OH+

BuLi

THF-HMPA

-20 oC+

1 TBAF2 H2 Pd(OH)2C

112 65 113 100

110

111

O

OBnCHO

OBnBnO

O

OBn

BnOBnO

O

OBnCH(OiPr)2

OBnH

O

OBnCH(OiPr)2

PPh3I-

OBn

O

OBn

BnOBnO

O

OBn

OBnH

O

OBnOBn

BnOH

O

OH

HOHO

O

OH

OH

O

OHOH

HO

++

BuLi

THF-HMPA

-20 oC

BuLi

THF-HMPA

-20 oC

TFA H2 O THF rt

115 49

116 R = CH(OiPr)2

117 R = CHO

118 45

H2 Pd(OH)2C

110

114

114

119


Scheme (25)

Scheme (26)

OBn

R1

R2

PPh3BF4-O

O

OOHC

O

O

O

O

O

O

O

O

HO

O

O

O

O

O O

OBn

R1

R2

O

O

O

O

O

O

H

O

OBn

R1

R2

O

O

O

O

O

O

O

O

OBn

R1

R2

O

O

O

+

BCl3 (005 equiv)

MS 4A CH2 Cl2 0 o C

+



R1 R2 = OBn H

120a - b

121

122a - b

123a - b

124

125a - b

OTBDPS

BnO X

SO Ph

O

BnO

OHCO

BnO

OMeOBn

OBn

O

BnO

OTBDPS

BnO

SO Ph

O

BnO

OMeOBn

OBn

O

HO

OMeOH

OHO

HOHO

OH

OH

128

229 74

1 RaNi (74)

2 BH3 DMS

NaOH H 2O2 (74)

3 H2 PdC (70)

130 74

LDA THF

-100 oC

126 X = H

127 X = Li


Scheme (27)

Scheme (28)










O

BnO

OTBDPS

BnO X

SO Ph

O

BnO

OBn

BnO Li

SO Ph

DMF

OHO

HOOH

OH

O OH

OH

HO

OHOH

O

BnO

OTBDPS

BnO

SO Ph

O

OBn

OBnOBnSO

Ph

OH

131 X = Li

132 X = CHO

THF -100 oC

1 Ra-Ni

2 BH3 DMS NaOH H2O2

3 H2 PdC

131

133

134

OBnO

OBnOMe

BnO

Li

OBnO

BnOOBn

OBn

OOBn

OBnOMeBnO

OH

OBnO

BnOOBn

OBn

O

n-BuLi

BnO

OMe

BnO

BrBr

O

OBn

OHO

OH

OH

HO

OHO

OH

HO

OMe

O

BnO

OMeOBn

O

BnO

139 92

1BF3 OEt2 EtOH

2 H2 PdC AcOH

140 52 over 2 steps

135 136 137

138

CBr4 PPh3








Scheme (29)

O

BnO

BnOOBn

OBn

OOBn

OBnOMe

OBnOH

O

BnO

BnO

OBn

OBn

O

O

BnOOBn

OMe

BnO

Li

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnOBnO

OBn

OBnBnO

O

BnO

BnO

OBn

O

OBnO

OBn

OBnBnO

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OMe



1 BF3 OEt2 Et3 OH

2 H2 PtO2 EtOAc

145 76

1 H2 SO4 AcOH

2 PCC

146 62

repeat steps

repeat st eps

141 142

143

147

148


Scheme (30)

Scheme (31)

O

BnOOBn

OMe

Li

BnO

OPivBnO

OBn

OBn

BnO

O OO

BF3 OEt2

OBnO

OBn

OBn

BnO

OO

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

CAN

OBnO

OBn

OBn

BnO

OO

OO

BnOOBn

BnO

OMe

OHBnO

OBn

OBn

BnO

OHO

O

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

OPivBnO

OBn

OBn

BnO

OH OO

O

OMe

BnOOBn

BnO

OAcO

OAc

OAc

AcO

OAcOAc

OAcO

OAc

AcO

OMe

1

2 NaOMe MeOH


with a-isomer

1 Et3N Pyr H2O

2 H2 PdC H+

3 Ac2 O Pyr

149 151

152153

154 155

150

OBn

BnO

OBnO

OBn

BnO

OBnO

BnO

MeO

OBnO

OBn

BnO

O

OMe

AcO

OAcO

OAc

OAc

AcO

OAcO

OAc

O

BnOOBn

OMe

BnO

159 74 over 2 steps

+

BuLi ZnCl2 THF

1 H2 PdC2 Ac2O Pyr

156 157

158 59


Scheme (32)

Scheme (33)



OBnO

OBn

BnO

O

OBnO

ClZnO

OBn

BnOCl

R

OBnO

O

OBn

BnOCl

ZnR

O

ZnR

OBnO

OBn

BnO

160 161

162163

O

OBn

OBnBnO

O

O

OBn

OBnBnO H

TMS

O

OBn

OBnBnO H

O

OBn

BnO

OBnHO

O

OBn

OBnBnO OH

TMS

OBnBnO HO

OBn

TMS

O

OR

ORRO H

O

OR

RO

OR

OBn

OBnBnO

H

TMS

O+

K2CO3 MeOH

1 n-BuLi THF -78 oC

2 164

164165 66

166α 60 166β 13167 97


168 85

169 R = Bn 83


H2 (1 atm)Pd(OH) 2C

TMS-acetyl ene


-78 o C


O

OHCOBn

OBnBnO

OMe

O

CO2MeAcO

OAcAcHN

OAc

SO2

NAcO

OBnH

H

OBn

OBn

H

O

OMeH HH

A

O

CO2MeAcO

OAcAcHN

OAc

O

OBnOMe

OBnOBn

HO

AcO

+

Nu

174175

176

SmI2 THF

Scheme (34)

Scheme (35)

Scheme (36)

O

BnO

BnO

BnO

Si lylO

O2S N

O

BnO

HO R2R1

BnOBnO

SilylO

OBnO

BnO

BnO

SilylO

Sm(III)

R1COR2 SmI2 THF

171 172

173

NHBoc

OAcO

AcO

AcHN O

O

CO2BnO

OO

OO

OH

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

R2

O

CO2Me

AcHN

OAc

AcO

R1

AcO

AcO

AcHNO CO2Bn

NHBoc

AcO

OAc

O

Zn(BH4)2

180 R1 R2 = H OH ( RS 11)

181 R1 R2 = O

182 R1 = H R2 = OH de gt 90

DMSO Ac2O

177178

179

13 steps

22 equiv SmI2 THF


Scheme (37)

Fig (2)




4 CATIONIC METHODS


OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO


+

Ac2O Pyr

187 X = OMP

188 X = SPh 73



+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3















Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331





































































Scheme (9)

Scheme (10)

OAcO

AcOOAc

OAc

NO2O

OH

O

O

OO

OHO

HOOH

OH

O

HO

HOOH

OH

Bu3 SnH

OAcO

AcOOAc

OAc

NO2

OO

O

OO

OH

OAcO

AcOOAc

OAc

X

OO

O

OO

KF 18-C-6 MeCN


38 X = NO 2

39 X = H 57

1 NaOMe

2 H3O+

36

33

37

40 89 over 2 st eps

CHO

O

O

O

O

CH2OPiv

OAcO

AcOOAc

OAc

NO2

OHO

HOOH

OH

O OH

OH

HO

OH

OAcO

AcOOAc

OAc

NO2

PivO

OH

O

O

O

O

OAcO

AcOOAc

OAc

NO2

PivO

O

O

O

O


1 AcOH

2 Ac2O-BF3 OEt

KF 18-C-6 MeCN

41 36

42

4344

3 Bu3SnH AIBN

4 NaOMe

5 H3O+







Scheme (11)

Scheme (12)

OBnO

OBnOMe

BnO

NO2

OBnO

OBn

BnO

OBn

CHO

OHO

OH

HO

OH

OHO

OHOMe

HO

OBnO

OBn

BnO

OBn

OBnO

OBnOMe

BnO

NO2R

OBnO

OBn

BnO

OBn

OBnO

OBnOMe

BnO

KF 18-C-6 MeCN+

1 n-BuLi2 PTC-Cl

51 R = OH

52 R = OC(S)OPh

Bu3 SnH AIBN

1 TsNHNH NaOAc

2 Na NH3

49

50

5354

OAcO

OAc

AcOO

OAcO

OAc

OAc

NO2OAc

OAc

AcO

OAcO

BnOOBn

OMe

BnO

OO

AcOOAc

OAc

OAcO

OMe

BnO O

BnOOBn

O

OO

AcOOAc

OAc

NO2

OAcO

OAc

AcO

OAcO

BnOOBn

OMe

BnO

OH

KF 18-C-6 MeCN


5 NaOMe MeOH

45

46

47

48





Scheme (13)

Scheme (14)

BnO

OBn

O2N

OMe

O

CHO

OBnO

OBn

BnO

OMe

OHO

OH

OHO

OH

HO

OMe

OBnO

OBn

OBnO

OBn

BnO

HO

NO2

OMe

OBnO

OBn

OBnO

OBn

BnO

X

+

KF 18-C-6 MeCN


58 X = NO 2


Bu3SnH AIBN

Pd(OH)2 H2

rt 1 atm 24 h

40

60 74

55

56

57

O

BnOOBn

BnO

OBn

OH

O

OHNO2

O

O

BnOOBn

BnO

OBn

OH

O

ONO2

O

O

O

O

O

AcOOAc

AcO

OAc

O

OAc OAc

OAc

O

BnOOBn

BnO

OBn

NO2OH

Et3 N MeCN

1Bu3 SnH AIBN

2 BF OEt Et3SH

3 L-SelectrideTHF

64 61 in 3 steps

1 Pd(OH)2 C6 H10

2 Ac2O TESOTF

61 63 43

62

65




Scheme (15)

Scheme (16)

OBnO

BnO

H

OBn

OH

OOBn

BnO

OBn

OBn

BnO

OBn

OBn

OBnO

BnO

OBn

OH

SO2

O

OBn

O O

AcO

AcO

AcO

OAc

OAc

OAc

OAc

OAc

OBnO

BnO

OBn

OH

I

O

HS

OBn

BnO

OBn

OBn

68 90 over 2 steps

KOH CCl4 t-BuOH H2O

1 H2 PdC

2 Ac2O Pyr

70 69 over 2 steps

+

1 K2CO3

2 mCPA66

67

69

O

BnOOBn

BnO

OBn

OH

(EtO)2P(O)CH2CO2Et

OBn

OBn

OBnO

OBn

OBnO

BnOOBn

OBn

X

O OBn

OBn

BnOOBn

OBnO

BnOOBn

OBn

OBnO

BnOOBn

OBn

R

OBnO

BnOOBn

OBn

SH

LiAlH4

OAc

AcOOAc

O OAcOAcOAcO

OAc

OAc

1 H2 Pd(OH)2C

2 Ac2 O Pyr

NaH THF

72 R = CO2Et

73 R = CH2OH

66 over 3 steps

K2CO3 acetone

76 X = S

77 X = SO2 79

Oxone THF MeOH H2 O

KOH CCl4 aq tBuOH

78 57ZE 8812

79

71

75





Scheme (17)

Scheme (18)

O

O O

O

O OH

O OMe

OBnBnO

SO2

P

EtO

EtO

O

OBn

O

OMe

OAc

OAc

OAcO

O O

O

O

O

OO OMe

OBnBnO

SO2

OBn

O

O O

O

O O

O

O

O

OMe

OBn

OBn

OBn

83 50 E only

80

+

NaH THF -78 oC

82 86αβ 11

KOHAl2O3

CBr2F2 CH2Cl2

tBuOH 5 oC

2 h

1 H2PdC EtOAc RT 7h

2 Ac2 O Pyr RT

84 69 over 2 st eps

81

O

O O

O

O OH POEt

OEt

O

SO2

P

EtO

EtOO

O

O

O

OO

O

O

O

O O

O

O

O O

O

O

O

O SO2

O

O

O

O

O

O O

O

OO

O

O

85 75βαββ ca 31

86 66β αββ = 141 E only

H2PdC EtOAc

87 76βαβ β = 141

21 NaH THF -78 o C

80 (2 equiv)











25 C-1 Vinyl Anions


Scheme (19)

OCH3

O O

OPhS

PhS

O O

OO

OCH3

O O

OO O

O H

OCH3

O O

OPhSPhS

O O

O OH

OCH3

O O

OO O

O OH

+

n-BuLi THF -78 oC


Et3SiH BF3 OEt2

90 77


-78 oC

88

89







Scheme (20)

Scheme (21)

OO O

O

O CHO

O

BnOOBn

BnO

OBn

CHO

OBn

CHO

BnO

O

BnOBnO

O

BnOOBn

BnO OBn

CHO

PPh3I-

OO

O

OO

O

OMeOBn

OBn

OBn

PPh3I-

OCHO

O

PPh3I-

ORRO

RO

OO

ORRHO

OO

OR

+ +

+

( 93 - 96 )

( 97 - 98 )

BuLi THF-HMPA

-30 iexclaelig

99

Reduction

100

+

93 9495

96 97 98

O

OBnBnO

BnO

OO

O

OO

HO

O

O

OO

PPh3I-

O

OHHO

HO

O

HOOH OH

HO

OBnBnO

CHO

BnO

O

+

BuLi THF-HMPA

-30 oC

1 p-MeC 6H4SO2-

NH2NH2 AcONa

2 H2 Pd(OH)2 3 bar

3 Amberli te H+

+

10197

102

103





Scheme (22)

O

BnOOBn

BnO OTBDPS

PPh3I-

BnO

H

O

BnOOBn

OTBDPS

OO

O

OO

O

CHOO

O

OO

O

BnO

O

BnOOBn

BnO

OO

O

OO

H

HOBn

BnO OTBDPS

O

BnOOBn

BnO O

OO

O

OO

H

OBn

BnO OTBDPS

PPh3I-

O

BnO

O

BnOOBn

BnO OTBDPS

PPh3I-

O

AcOOAc

AcO

O

AcOOAc

AcO

OO

O

OO

O

AcOOAc

AcO OAc

O

BnOOBn

BnO

O

BnOOBn

BnO

OO

O

OO

H

H

O

BnOOBn

BnO OTBDPS

H

1 TBAF2 PCC

+107 36

+

1 TBAF2 PCC3

+


104

33

105

106104

104

108109

BuLi THF-HMPA

-50 o C

70EZ 19

BuLi THF-HMPA

-50 o C







Scheme (23)

Scheme (24)

BnOO

OBnCHO

OBn

O

OBn

PPh3I-

OBn

OBn

O

OBn

BnOBnO

O

OBnOBn

OBnH

O

OH

HOHO

O

OHOH

OH+

BuLi

THF-HMPA

-20 oC+

1 TBAF2 H2 Pd(OH)2C

112 65 113 100

110

111

O

OBnCHO

OBnBnO

O

OBn

BnOBnO

O

OBnCH(OiPr)2

OBnH

O

OBnCH(OiPr)2

PPh3I-

OBn

O

OBn

BnOBnO

O

OBn

OBnH

O

OBnOBn

BnOH

O

OH

HOHO

O

OH

OH

O

OHOH

HO

++

BuLi

THF-HMPA

-20 oC

BuLi

THF-HMPA

-20 oC

TFA H2 O THF rt

115 49

116 R = CH(OiPr)2

117 R = CHO

118 45

H2 Pd(OH)2C

110

114

114

119


Scheme (25)

Scheme (26)

OBn

R1

R2

PPh3BF4-O

O

OOHC

O

O

O

O

O

O

O

O

HO

O

O

O

O

O O

OBn

R1

R2

O

O

O

O

O

O

H

O

OBn

R1

R2

O

O

O

O

O

O

O

O

OBn

R1

R2

O

O

O

+

BCl3 (005 equiv)

MS 4A CH2 Cl2 0 o C

+



R1 R2 = OBn H

120a - b

121

122a - b

123a - b

124

125a - b

OTBDPS

BnO X

SO Ph

O

BnO

OHCO

BnO

OMeOBn

OBn

O

BnO

OTBDPS

BnO

SO Ph

O

BnO

OMeOBn

OBn

O

HO

OMeOH

OHO

HOHO

OH

OH

128

229 74

1 RaNi (74)

2 BH3 DMS

NaOH H 2O2 (74)

3 H2 PdC (70)

130 74

LDA THF

-100 oC

126 X = H

127 X = Li


Scheme (27)

Scheme (28)










O

BnO

OTBDPS

BnO X

SO Ph

O

BnO

OBn

BnO Li

SO Ph

DMF

OHO

HOOH

OH

O OH

OH

HO

OHOH

O

BnO

OTBDPS

BnO

SO Ph

O

OBn

OBnOBnSO

Ph

OH

131 X = Li

132 X = CHO

THF -100 oC

1 Ra-Ni

2 BH3 DMS NaOH H2O2

3 H2 PdC

131

133

134

OBnO

OBnOMe

BnO

Li

OBnO

BnOOBn

OBn

OOBn

OBnOMeBnO

OH

OBnO

BnOOBn

OBn

O

n-BuLi

BnO

OMe

BnO

BrBr

O

OBn

OHO

OH

OH

HO

OHO

OH

HO

OMe

O

BnO

OMeOBn

O

BnO

139 92

1BF3 OEt2 EtOH

2 H2 PdC AcOH

140 52 over 2 steps

135 136 137

138

CBr4 PPh3








Scheme (29)

O

BnO

BnOOBn

OBn

OOBn

OBnOMe

OBnOH

O

BnO

BnO

OBn

OBn

O

O

BnOOBn

OMe

BnO

Li

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnOBnO

OBn

OBnBnO

O

BnO

BnO

OBn

O

OBnO

OBn

OBnBnO

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OMe



1 BF3 OEt2 Et3 OH

2 H2 PtO2 EtOAc

145 76

1 H2 SO4 AcOH

2 PCC

146 62

repeat steps

repeat st eps

141 142

143

147

148


Scheme (30)

Scheme (31)

O

BnOOBn

OMe

Li

BnO

OPivBnO

OBn

OBn

BnO

O OO

BF3 OEt2

OBnO

OBn

OBn

BnO

OO

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

CAN

OBnO

OBn

OBn

BnO

OO

OO

BnOOBn

BnO

OMe

OHBnO

OBn

OBn

BnO

OHO

O

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

OPivBnO

OBn

OBn

BnO

OH OO

O

OMe

BnOOBn

BnO

OAcO

OAc

OAc

AcO

OAcOAc

OAcO

OAc

AcO

OMe

1

2 NaOMe MeOH


with a-isomer

1 Et3N Pyr H2O

2 H2 PdC H+

3 Ac2 O Pyr

149 151

152153

154 155

150

OBn

BnO

OBnO

OBn

BnO

OBnO

BnO

MeO

OBnO

OBn

BnO

O

OMe

AcO

OAcO

OAc

OAc

AcO

OAcO

OAc

O

BnOOBn

OMe

BnO

159 74 over 2 steps

+

BuLi ZnCl2 THF

1 H2 PdC2 Ac2O Pyr

156 157

158 59


Scheme (32)

Scheme (33)



OBnO

OBn

BnO

O

OBnO

ClZnO

OBn

BnOCl

R

OBnO

O

OBn

BnOCl

ZnR

O

ZnR

OBnO

OBn

BnO

160 161

162163

O

OBn

OBnBnO

O

O

OBn

OBnBnO H

TMS

O

OBn

OBnBnO H

O

OBn

BnO

OBnHO

O

OBn

OBnBnO OH

TMS

OBnBnO HO

OBn

TMS

O

OR

ORRO H

O

OR

RO

OR

OBn

OBnBnO

H

TMS

O+

K2CO3 MeOH

1 n-BuLi THF -78 oC

2 164

164165 66

166α 60 166β 13167 97


168 85

169 R = Bn 83


H2 (1 atm)Pd(OH) 2C

TMS-acetyl ene


-78 o C


O

OHCOBn

OBnBnO

OMe

O

CO2MeAcO

OAcAcHN

OAc

SO2

NAcO

OBnH

H

OBn

OBn

H

O

OMeH HH

A

O

CO2MeAcO

OAcAcHN

OAc

O

OBnOMe

OBnOBn

HO

AcO

+

Nu

174175

176

SmI2 THF

Scheme (34)

Scheme (35)

Scheme (36)

O

BnO

BnO

BnO

Si lylO

O2S N

O

BnO

HO R2R1

BnOBnO

SilylO

OBnO

BnO

BnO

SilylO

Sm(III)

R1COR2 SmI2 THF

171 172

173

NHBoc

OAcO

AcO

AcHN O

O

CO2BnO

OO

OO

OH

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

R2

O

CO2Me

AcHN

OAc

AcO

R1

AcO

AcO

AcHNO CO2Bn

NHBoc

AcO

OAc

O

Zn(BH4)2

180 R1 R2 = H OH ( RS 11)

181 R1 R2 = O

182 R1 = H R2 = OH de gt 90

DMSO Ac2O

177178

179

13 steps

22 equiv SmI2 THF


Scheme (37)

Fig (2)




4 CATIONIC METHODS


OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO


+

Ac2O Pyr

187 X = OMP

188 X = SPh 73



+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3















Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331






































































Scheme (11)

Scheme (12)

OBnO

OBnOMe

BnO

NO2

OBnO

OBn

BnO

OBn

CHO

OHO

OH

HO

OH

OHO

OHOMe

HO

OBnO

OBn

BnO

OBn

OBnO

OBnOMe

BnO

NO2R

OBnO

OBn

BnO

OBn

OBnO

OBnOMe

BnO

KF 18-C-6 MeCN+

1 n-BuLi2 PTC-Cl

51 R = OH

52 R = OC(S)OPh

Bu3 SnH AIBN

1 TsNHNH NaOAc

2 Na NH3

49

50

5354

OAcO

OAc

AcOO

OAcO

OAc

OAc

NO2OAc

OAc

AcO

OAcO

BnOOBn

OMe

BnO

OO

AcOOAc

OAc

OAcO

OMe

BnO O

BnOOBn

O

OO

AcOOAc

OAc

NO2

OAcO

OAc

AcO

OAcO

BnOOBn

OMe

BnO

OH

KF 18-C-6 MeCN


5 NaOMe MeOH

45

46

47

48





Scheme (13)

Scheme (14)

BnO

OBn

O2N

OMe

O

CHO

OBnO

OBn

BnO

OMe

OHO

OH

OHO

OH

HO

OMe

OBnO

OBn

OBnO

OBn

BnO

HO

NO2

OMe

OBnO

OBn

OBnO

OBn

BnO

X

+

KF 18-C-6 MeCN


58 X = NO 2


Bu3SnH AIBN

Pd(OH)2 H2

rt 1 atm 24 h

40

60 74

55

56

57

O

BnOOBn

BnO

OBn

OH

O

OHNO2

O

O

BnOOBn

BnO

OBn

OH

O

ONO2

O

O

O

O

O

AcOOAc

AcO

OAc

O

OAc OAc

OAc

O

BnOOBn

BnO

OBn

NO2OH

Et3 N MeCN

1Bu3 SnH AIBN

2 BF OEt Et3SH

3 L-SelectrideTHF

64 61 in 3 steps

1 Pd(OH)2 C6 H10

2 Ac2O TESOTF

61 63 43

62

65




Scheme (15)

Scheme (16)

OBnO

BnO

H

OBn

OH

OOBn

BnO

OBn

OBn

BnO

OBn

OBn

OBnO

BnO

OBn

OH

SO2

O

OBn

O O

AcO

AcO

AcO

OAc

OAc

OAc

OAc

OAc

OBnO

BnO

OBn

OH

I

O

HS

OBn

BnO

OBn

OBn

68 90 over 2 steps

KOH CCl4 t-BuOH H2O

1 H2 PdC

2 Ac2O Pyr

70 69 over 2 steps

+

1 K2CO3

2 mCPA66

67

69

O

BnOOBn

BnO

OBn

OH

(EtO)2P(O)CH2CO2Et

OBn

OBn

OBnO

OBn

OBnO

BnOOBn

OBn

X

O OBn

OBn

BnOOBn

OBnO

BnOOBn

OBn

OBnO

BnOOBn

OBn

R

OBnO

BnOOBn

OBn

SH

LiAlH4

OAc

AcOOAc

O OAcOAcOAcO

OAc

OAc

1 H2 Pd(OH)2C

2 Ac2 O Pyr

NaH THF

72 R = CO2Et

73 R = CH2OH

66 over 3 steps

K2CO3 acetone

76 X = S

77 X = SO2 79

Oxone THF MeOH H2 O

KOH CCl4 aq tBuOH

78 57ZE 8812

79

71

75





Scheme (17)

Scheme (18)

O

O O

O

O OH

O OMe

OBnBnO

SO2

P

EtO

EtO

O

OBn

O

OMe

OAc

OAc

OAcO

O O

O

O

O

OO OMe

OBnBnO

SO2

OBn

O

O O

O

O O

O

O

O

OMe

OBn

OBn

OBn

83 50 E only

80

+

NaH THF -78 oC

82 86αβ 11

KOHAl2O3

CBr2F2 CH2Cl2

tBuOH 5 oC

2 h

1 H2PdC EtOAc RT 7h

2 Ac2 O Pyr RT

84 69 over 2 st eps

81

O

O O

O

O OH POEt

OEt

O

SO2

P

EtO

EtOO

O

O

O

OO

O

O

O

O O

O

O

O O

O

O

O

O SO2

O

O

O

O

O

O O

O

OO

O

O

85 75βαββ ca 31

86 66β αββ = 141 E only

H2PdC EtOAc

87 76βαβ β = 141

21 NaH THF -78 o C

80 (2 equiv)











25 C-1 Vinyl Anions


Scheme (19)

OCH3

O O

OPhS

PhS

O O

OO

OCH3

O O

OO O

O H

OCH3

O O

OPhSPhS

O O

O OH

OCH3

O O

OO O

O OH

+

n-BuLi THF -78 oC


Et3SiH BF3 OEt2

90 77


-78 oC

88

89







Scheme (20)

Scheme (21)

OO O

O

O CHO

O

BnOOBn

BnO

OBn

CHO

OBn

CHO

BnO

O

BnOBnO

O

BnOOBn

BnO OBn

CHO

PPh3I-

OO

O

OO

O

OMeOBn

OBn

OBn

PPh3I-

OCHO

O

PPh3I-

ORRO

RO

OO

ORRHO

OO

OR

+ +

+

( 93 - 96 )

( 97 - 98 )

BuLi THF-HMPA

-30 iexclaelig

99

Reduction

100

+

93 9495

96 97 98

O

OBnBnO

BnO

OO

O

OO

HO

O

O

OO

PPh3I-

O

OHHO

HO

O

HOOH OH

HO

OBnBnO

CHO

BnO

O

+

BuLi THF-HMPA

-30 oC

1 p-MeC 6H4SO2-

NH2NH2 AcONa

2 H2 Pd(OH)2 3 bar

3 Amberli te H+

+

10197

102

103





Scheme (22)

O

BnOOBn

BnO OTBDPS

PPh3I-

BnO

H

O

BnOOBn

OTBDPS

OO

O

OO

O

CHOO

O

OO

O

BnO

O

BnOOBn

BnO

OO

O

OO

H

HOBn

BnO OTBDPS

O

BnOOBn

BnO O

OO

O

OO

H

OBn

BnO OTBDPS

PPh3I-

O

BnO

O

BnOOBn

BnO OTBDPS

PPh3I-

O

AcOOAc

AcO

O

AcOOAc

AcO

OO

O

OO

O

AcOOAc

AcO OAc

O

BnOOBn

BnO

O

BnOOBn

BnO

OO

O

OO

H

H

O

BnOOBn

BnO OTBDPS

H

1 TBAF2 PCC

+107 36

+

1 TBAF2 PCC3

+


104

33

105

106104

104

108109

BuLi THF-HMPA

-50 o C

70EZ 19

BuLi THF-HMPA

-50 o C







Scheme (23)

Scheme (24)

BnOO

OBnCHO

OBn

O

OBn

PPh3I-

OBn

OBn

O

OBn

BnOBnO

O

OBnOBn

OBnH

O

OH

HOHO

O

OHOH

OH+

BuLi

THF-HMPA

-20 oC+

1 TBAF2 H2 Pd(OH)2C

112 65 113 100

110

111

O

OBnCHO

OBnBnO

O

OBn

BnOBnO

O

OBnCH(OiPr)2

OBnH

O

OBnCH(OiPr)2

PPh3I-

OBn

O

OBn

BnOBnO

O

OBn

OBnH

O

OBnOBn

BnOH

O

OH

HOHO

O

OH

OH

O

OHOH

HO

++

BuLi

THF-HMPA

-20 oC

BuLi

THF-HMPA

-20 oC

TFA H2 O THF rt

115 49

116 R = CH(OiPr)2

117 R = CHO

118 45

H2 Pd(OH)2C

110

114

114

119


Scheme (25)

Scheme (26)

OBn

R1

R2

PPh3BF4-O

O

OOHC

O

O

O

O

O

O

O

O

HO

O

O

O

O

O O

OBn

R1

R2

O

O

O

O

O

O

H

O

OBn

R1

R2

O

O

O

O

O

O

O

O

OBn

R1

R2

O

O

O

+

BCl3 (005 equiv)

MS 4A CH2 Cl2 0 o C

+



R1 R2 = OBn H

120a - b

121

122a - b

123a - b

124

125a - b

OTBDPS

BnO X

SO Ph

O

BnO

OHCO

BnO

OMeOBn

OBn

O

BnO

OTBDPS

BnO

SO Ph

O

BnO

OMeOBn

OBn

O

HO

OMeOH

OHO

HOHO

OH

OH

128

229 74

1 RaNi (74)

2 BH3 DMS

NaOH H 2O2 (74)

3 H2 PdC (70)

130 74

LDA THF

-100 oC

126 X = H

127 X = Li


Scheme (27)

Scheme (28)










O

BnO

OTBDPS

BnO X

SO Ph

O

BnO

OBn

BnO Li

SO Ph

DMF

OHO

HOOH

OH

O OH

OH

HO

OHOH

O

BnO

OTBDPS

BnO

SO Ph

O

OBn

OBnOBnSO

Ph

OH

131 X = Li

132 X = CHO

THF -100 oC

1 Ra-Ni

2 BH3 DMS NaOH H2O2

3 H2 PdC

131

133

134

OBnO

OBnOMe

BnO

Li

OBnO

BnOOBn

OBn

OOBn

OBnOMeBnO

OH

OBnO

BnOOBn

OBn

O

n-BuLi

BnO

OMe

BnO

BrBr

O

OBn

OHO

OH

OH

HO

OHO

OH

HO

OMe

O

BnO

OMeOBn

O

BnO

139 92

1BF3 OEt2 EtOH

2 H2 PdC AcOH

140 52 over 2 steps

135 136 137

138

CBr4 PPh3








Scheme (29)

O

BnO

BnOOBn

OBn

OOBn

OBnOMe

OBnOH

O

BnO

BnO

OBn

OBn

O

O

BnOOBn

OMe

BnO

Li

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnOBnO

OBn

OBnBnO

O

BnO

BnO

OBn

O

OBnO

OBn

OBnBnO

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OMe



1 BF3 OEt2 Et3 OH

2 H2 PtO2 EtOAc

145 76

1 H2 SO4 AcOH

2 PCC

146 62

repeat steps

repeat st eps

141 142

143

147

148


Scheme (30)

Scheme (31)

O

BnOOBn

OMe

Li

BnO

OPivBnO

OBn

OBn

BnO

O OO

BF3 OEt2

OBnO

OBn

OBn

BnO

OO

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

CAN

OBnO

OBn

OBn

BnO

OO

OO

BnOOBn

BnO

OMe

OHBnO

OBn

OBn

BnO

OHO

O

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

OPivBnO

OBn

OBn

BnO

OH OO

O

OMe

BnOOBn

BnO

OAcO

OAc

OAc

AcO

OAcOAc

OAcO

OAc

AcO

OMe

1

2 NaOMe MeOH


with a-isomer

1 Et3N Pyr H2O

2 H2 PdC H+

3 Ac2 O Pyr

149 151

152153

154 155

150

OBn

BnO

OBnO

OBn

BnO

OBnO

BnO

MeO

OBnO

OBn

BnO

O

OMe

AcO

OAcO

OAc

OAc

AcO

OAcO

OAc

O

BnOOBn

OMe

BnO

159 74 over 2 steps

+

BuLi ZnCl2 THF

1 H2 PdC2 Ac2O Pyr

156 157

158 59


Scheme (32)

Scheme (33)



OBnO

OBn

BnO

O

OBnO

ClZnO

OBn

BnOCl

R

OBnO

O

OBn

BnOCl

ZnR

O

ZnR

OBnO

OBn

BnO

160 161

162163

O

OBn

OBnBnO

O

O

OBn

OBnBnO H

TMS

O

OBn

OBnBnO H

O

OBn

BnO

OBnHO

O

OBn

OBnBnO OH

TMS

OBnBnO HO

OBn

TMS

O

OR

ORRO H

O

OR

RO

OR

OBn

OBnBnO

H

TMS

O+

K2CO3 MeOH

1 n-BuLi THF -78 oC

2 164

164165 66

166α 60 166β 13167 97


168 85

169 R = Bn 83


H2 (1 atm)Pd(OH) 2C

TMS-acetyl ene


-78 o C


O

OHCOBn

OBnBnO

OMe

O

CO2MeAcO

OAcAcHN

OAc

SO2

NAcO

OBnH

H

OBn

OBn

H

O

OMeH HH

A

O

CO2MeAcO

OAcAcHN

OAc

O

OBnOMe

OBnOBn

HO

AcO

+

Nu

174175

176

SmI2 THF

Scheme (34)

Scheme (35)

Scheme (36)

O

BnO

BnO

BnO

Si lylO

O2S N

O

BnO

HO R2R1

BnOBnO

SilylO

OBnO

BnO

BnO

SilylO

Sm(III)

R1COR2 SmI2 THF

171 172

173

NHBoc

OAcO

AcO

AcHN O

O

CO2BnO

OO

OO

OH

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

R2

O

CO2Me

AcHN

OAc

AcO

R1

AcO

AcO

AcHNO CO2Bn

NHBoc

AcO

OAc

O

Zn(BH4)2

180 R1 R2 = H OH ( RS 11)

181 R1 R2 = O

182 R1 = H R2 = OH de gt 90

DMSO Ac2O

177178

179

13 steps

22 equiv SmI2 THF


Scheme (37)

Fig (2)




4 CATIONIC METHODS


OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO


+

Ac2O Pyr

187 X = OMP

188 X = SPh 73



+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3















Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331




































































Scheme (13)

Scheme (14)

BnO

OBn

O2N

OMe

O

CHO

OBnO

OBn

BnO

OMe

OHO

OH

OHO

OH

HO

OMe

OBnO

OBn

OBnO

OBn

BnO

HO

NO2

OMe

OBnO

OBn

OBnO

OBn

BnO

X

+

KF 18-C-6 MeCN


58 X = NO 2


Bu3SnH AIBN

Pd(OH)2 H2

rt 1 atm 24 h

40

60 74

55

56

57

O

BnOOBn

BnO

OBn

OH

O

OHNO2

O

O

BnOOBn

BnO

OBn

OH

O

ONO2

O

O

O

O

O

AcOOAc

AcO

OAc

O

OAc OAc

OAc

O

BnOOBn

BnO

OBn

NO2OH

Et3 N MeCN

1Bu3 SnH AIBN

2 BF OEt Et3SH

3 L-SelectrideTHF

64 61 in 3 steps

1 Pd(OH)2 C6 H10

2 Ac2O TESOTF

61 63 43

62

65




Scheme (15)

Scheme (16)

OBnO

BnO

H

OBn

OH

OOBn

BnO

OBn

OBn

BnO

OBn

OBn

OBnO

BnO

OBn

OH

SO2

O

OBn

O O

AcO

AcO

AcO

OAc

OAc

OAc

OAc

OAc

OBnO

BnO

OBn

OH

I

O

HS

OBn

BnO

OBn

OBn

68 90 over 2 steps

KOH CCl4 t-BuOH H2O

1 H2 PdC

2 Ac2O Pyr

70 69 over 2 steps

+

1 K2CO3

2 mCPA66

67

69

O

BnOOBn

BnO

OBn

OH

(EtO)2P(O)CH2CO2Et

OBn

OBn

OBnO

OBn

OBnO

BnOOBn

OBn

X

O OBn

OBn

BnOOBn

OBnO

BnOOBn

OBn

OBnO

BnOOBn

OBn

R

OBnO

BnOOBn

OBn

SH

LiAlH4

OAc

AcOOAc

O OAcOAcOAcO

OAc

OAc

1 H2 Pd(OH)2C

2 Ac2 O Pyr

NaH THF

72 R = CO2Et

73 R = CH2OH

66 over 3 steps

K2CO3 acetone

76 X = S

77 X = SO2 79

Oxone THF MeOH H2 O

KOH CCl4 aq tBuOH

78 57ZE 8812

79

71

75





Scheme (17)

Scheme (18)

O

O O

O

O OH

O OMe

OBnBnO

SO2

P

EtO

EtO

O

OBn

O

OMe

OAc

OAc

OAcO

O O

O

O

O

OO OMe

OBnBnO

SO2

OBn

O

O O

O

O O

O

O

O

OMe

OBn

OBn

OBn

83 50 E only

80

+

NaH THF -78 oC

82 86αβ 11

KOHAl2O3

CBr2F2 CH2Cl2

tBuOH 5 oC

2 h

1 H2PdC EtOAc RT 7h

2 Ac2 O Pyr RT

84 69 over 2 st eps

81

O

O O

O

O OH POEt

OEt

O

SO2

P

EtO

EtOO

O

O

O

OO

O

O

O

O O

O

O

O O

O

O

O

O SO2

O

O

O

O

O

O O

O

OO

O

O

85 75βαββ ca 31

86 66β αββ = 141 E only

H2PdC EtOAc

87 76βαβ β = 141

21 NaH THF -78 o C

80 (2 equiv)











25 C-1 Vinyl Anions


Scheme (19)

OCH3

O O

OPhS

PhS

O O

OO

OCH3

O O

OO O

O H

OCH3

O O

OPhSPhS

O O

O OH

OCH3

O O

OO O

O OH

+

n-BuLi THF -78 oC


Et3SiH BF3 OEt2

90 77


-78 oC

88

89







Scheme (20)

Scheme (21)

OO O

O

O CHO

O

BnOOBn

BnO

OBn

CHO

OBn

CHO

BnO

O

BnOBnO

O

BnOOBn

BnO OBn

CHO

PPh3I-

OO

O

OO

O

OMeOBn

OBn

OBn

PPh3I-

OCHO

O

PPh3I-

ORRO

RO

OO

ORRHO

OO

OR

+ +

+

( 93 - 96 )

( 97 - 98 )

BuLi THF-HMPA

-30 iexclaelig

99

Reduction

100

+

93 9495

96 97 98

O

OBnBnO

BnO

OO

O

OO

HO

O

O

OO

PPh3I-

O

OHHO

HO

O

HOOH OH

HO

OBnBnO

CHO

BnO

O

+

BuLi THF-HMPA

-30 oC

1 p-MeC 6H4SO2-

NH2NH2 AcONa

2 H2 Pd(OH)2 3 bar

3 Amberli te H+

+

10197

102

103





Scheme (22)

O

BnOOBn

BnO OTBDPS

PPh3I-

BnO

H

O

BnOOBn

OTBDPS

OO

O

OO

O

CHOO

O

OO

O

BnO

O

BnOOBn

BnO

OO

O

OO

H

HOBn

BnO OTBDPS

O

BnOOBn

BnO O

OO

O

OO

H

OBn

BnO OTBDPS

PPh3I-

O

BnO

O

BnOOBn

BnO OTBDPS

PPh3I-

O

AcOOAc

AcO

O

AcOOAc

AcO

OO

O

OO

O

AcOOAc

AcO OAc

O

BnOOBn

BnO

O

BnOOBn

BnO

OO

O

OO

H

H

O

BnOOBn

BnO OTBDPS

H

1 TBAF2 PCC

+107 36

+

1 TBAF2 PCC3

+


104

33

105

106104

104

108109

BuLi THF-HMPA

-50 o C

70EZ 19

BuLi THF-HMPA

-50 o C







Scheme (23)

Scheme (24)

BnOO

OBnCHO

OBn

O

OBn

PPh3I-

OBn

OBn

O

OBn

BnOBnO

O

OBnOBn

OBnH

O

OH

HOHO

O

OHOH

OH+

BuLi

THF-HMPA

-20 oC+

1 TBAF2 H2 Pd(OH)2C

112 65 113 100

110

111

O

OBnCHO

OBnBnO

O

OBn

BnOBnO

O

OBnCH(OiPr)2

OBnH

O

OBnCH(OiPr)2

PPh3I-

OBn

O

OBn

BnOBnO

O

OBn

OBnH

O

OBnOBn

BnOH

O

OH

HOHO

O

OH

OH

O

OHOH

HO

++

BuLi

THF-HMPA

-20 oC

BuLi

THF-HMPA

-20 oC

TFA H2 O THF rt

115 49

116 R = CH(OiPr)2

117 R = CHO

118 45

H2 Pd(OH)2C

110

114

114

119


Scheme (25)

Scheme (26)

OBn

R1

R2

PPh3BF4-O

O

OOHC

O

O

O

O

O

O

O

O

HO

O

O

O

O

O O

OBn

R1

R2

O

O

O

O

O

O

H

O

OBn

R1

R2

O

O

O

O

O

O

O

O

OBn

R1

R2

O

O

O

+

BCl3 (005 equiv)

MS 4A CH2 Cl2 0 o C

+



R1 R2 = OBn H

120a - b

121

122a - b

123a - b

124

125a - b

OTBDPS

BnO X

SO Ph

O

BnO

OHCO

BnO

OMeOBn

OBn

O

BnO

OTBDPS

BnO

SO Ph

O

BnO

OMeOBn

OBn

O

HO

OMeOH

OHO

HOHO

OH

OH

128

229 74

1 RaNi (74)

2 BH3 DMS

NaOH H 2O2 (74)

3 H2 PdC (70)

130 74

LDA THF

-100 oC

126 X = H

127 X = Li


Scheme (27)

Scheme (28)










O

BnO

OTBDPS

BnO X

SO Ph

O

BnO

OBn

BnO Li

SO Ph

DMF

OHO

HOOH

OH

O OH

OH

HO

OHOH

O

BnO

OTBDPS

BnO

SO Ph

O

OBn

OBnOBnSO

Ph

OH

131 X = Li

132 X = CHO

THF -100 oC

1 Ra-Ni

2 BH3 DMS NaOH H2O2

3 H2 PdC

131

133

134

OBnO

OBnOMe

BnO

Li

OBnO

BnOOBn

OBn

OOBn

OBnOMeBnO

OH

OBnO

BnOOBn

OBn

O

n-BuLi

BnO

OMe

BnO

BrBr

O

OBn

OHO

OH

OH

HO

OHO

OH

HO

OMe

O

BnO

OMeOBn

O

BnO

139 92

1BF3 OEt2 EtOH

2 H2 PdC AcOH

140 52 over 2 steps

135 136 137

138

CBr4 PPh3








Scheme (29)

O

BnO

BnOOBn

OBn

OOBn

OBnOMe

OBnOH

O

BnO

BnO

OBn

OBn

O

O

BnOOBn

OMe

BnO

Li

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnOBnO

OBn

OBnBnO

O

BnO

BnO

OBn

O

OBnO

OBn

OBnBnO

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OMe



1 BF3 OEt2 Et3 OH

2 H2 PtO2 EtOAc

145 76

1 H2 SO4 AcOH

2 PCC

146 62

repeat steps

repeat st eps

141 142

143

147

148


Scheme (30)

Scheme (31)

O

BnOOBn

OMe

Li

BnO

OPivBnO

OBn

OBn

BnO

O OO

BF3 OEt2

OBnO

OBn

OBn

BnO

OO

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

CAN

OBnO

OBn

OBn

BnO

OO

OO

BnOOBn

BnO

OMe

OHBnO

OBn

OBn

BnO

OHO

O

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

OPivBnO

OBn

OBn

BnO

OH OO

O

OMe

BnOOBn

BnO

OAcO

OAc

OAc

AcO

OAcOAc

OAcO

OAc

AcO

OMe

1

2 NaOMe MeOH


with a-isomer

1 Et3N Pyr H2O

2 H2 PdC H+

3 Ac2 O Pyr

149 151

152153

154 155

150

OBn

BnO

OBnO

OBn

BnO

OBnO

BnO

MeO

OBnO

OBn

BnO

O

OMe

AcO

OAcO

OAc

OAc

AcO

OAcO

OAc

O

BnOOBn

OMe

BnO

159 74 over 2 steps

+

BuLi ZnCl2 THF

1 H2 PdC2 Ac2O Pyr

156 157

158 59


Scheme (32)

Scheme (33)



OBnO

OBn

BnO

O

OBnO

ClZnO

OBn

BnOCl

R

OBnO

O

OBn

BnOCl

ZnR

O

ZnR

OBnO

OBn

BnO

160 161

162163

O

OBn

OBnBnO

O

O

OBn

OBnBnO H

TMS

O

OBn

OBnBnO H

O

OBn

BnO

OBnHO

O

OBn

OBnBnO OH

TMS

OBnBnO HO

OBn

TMS

O

OR

ORRO H

O

OR

RO

OR

OBn

OBnBnO

H

TMS

O+

K2CO3 MeOH

1 n-BuLi THF -78 oC

2 164

164165 66

166α 60 166β 13167 97


168 85

169 R = Bn 83


H2 (1 atm)Pd(OH) 2C

TMS-acetyl ene


-78 o C


O

OHCOBn

OBnBnO

OMe

O

CO2MeAcO

OAcAcHN

OAc

SO2

NAcO

OBnH

H

OBn

OBn

H

O

OMeH HH

A

O

CO2MeAcO

OAcAcHN

OAc

O

OBnOMe

OBnOBn

HO

AcO

+

Nu

174175

176

SmI2 THF

Scheme (34)

Scheme (35)

Scheme (36)

O

BnO

BnO

BnO

Si lylO

O2S N

O

BnO

HO R2R1

BnOBnO

SilylO

OBnO

BnO

BnO

SilylO

Sm(III)

R1COR2 SmI2 THF

171 172

173

NHBoc

OAcO

AcO

AcHN O

O

CO2BnO

OO

OO

OH

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

R2

O

CO2Me

AcHN

OAc

AcO

R1

AcO

AcO

AcHNO CO2Bn

NHBoc

AcO

OAc

O

Zn(BH4)2

180 R1 R2 = H OH ( RS 11)

181 R1 R2 = O

182 R1 = H R2 = OH de gt 90

DMSO Ac2O

177178

179

13 steps

22 equiv SmI2 THF


Scheme (37)

Fig (2)




4 CATIONIC METHODS


OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO


+

Ac2O Pyr

187 X = OMP

188 X = SPh 73



+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3















Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331



































































Scheme (15)

Scheme (16)

OBnO

BnO

H

OBn

OH

OOBn

BnO

OBn

OBn

BnO

OBn

OBn

OBnO

BnO

OBn

OH

SO2

O

OBn

O O

AcO

AcO

AcO

OAc

OAc

OAc

OAc

OAc

OBnO

BnO

OBn

OH

I

O

HS

OBn

BnO

OBn

OBn

68 90 over 2 steps

KOH CCl4 t-BuOH H2O

1 H2 PdC

2 Ac2O Pyr

70 69 over 2 steps

+

1 K2CO3

2 mCPA66

67

69

O

BnOOBn

BnO

OBn

OH

(EtO)2P(O)CH2CO2Et

OBn

OBn

OBnO

OBn

OBnO

BnOOBn

OBn

X

O OBn

OBn

BnOOBn

OBnO

BnOOBn

OBn

OBnO

BnOOBn

OBn

R

OBnO

BnOOBn

OBn

SH

LiAlH4

OAc

AcOOAc

O OAcOAcOAcO

OAc

OAc

1 H2 Pd(OH)2C

2 Ac2 O Pyr

NaH THF

72 R = CO2Et

73 R = CH2OH

66 over 3 steps

K2CO3 acetone

76 X = S

77 X = SO2 79

Oxone THF MeOH H2 O

KOH CCl4 aq tBuOH

78 57ZE 8812

79

71

75





Scheme (17)

Scheme (18)

O

O O

O

O OH

O OMe

OBnBnO

SO2

P

EtO

EtO

O

OBn

O

OMe

OAc

OAc

OAcO

O O

O

O

O

OO OMe

OBnBnO

SO2

OBn

O

O O

O

O O

O

O

O

OMe

OBn

OBn

OBn

83 50 E only

80

+

NaH THF -78 oC

82 86αβ 11

KOHAl2O3

CBr2F2 CH2Cl2

tBuOH 5 oC

2 h

1 H2PdC EtOAc RT 7h

2 Ac2 O Pyr RT

84 69 over 2 st eps

81

O

O O

O

O OH POEt

OEt

O

SO2

P

EtO

EtOO

O

O

O

OO

O

O

O

O O

O

O

O O

O

O

O

O SO2

O

O

O

O

O

O O

O

OO

O

O

85 75βαββ ca 31

86 66β αββ = 141 E only

H2PdC EtOAc

87 76βαβ β = 141

21 NaH THF -78 o C

80 (2 equiv)











25 C-1 Vinyl Anions


Scheme (19)

OCH3

O O

OPhS

PhS

O O

OO

OCH3

O O

OO O

O H

OCH3

O O

OPhSPhS

O O

O OH

OCH3

O O

OO O

O OH

+

n-BuLi THF -78 oC


Et3SiH BF3 OEt2

90 77


-78 oC

88

89







Scheme (20)

Scheme (21)

OO O

O

O CHO

O

BnOOBn

BnO

OBn

CHO

OBn

CHO

BnO

O

BnOBnO

O

BnOOBn

BnO OBn

CHO

PPh3I-

OO

O

OO

O

OMeOBn

OBn

OBn

PPh3I-

OCHO

O

PPh3I-

ORRO

RO

OO

ORRHO

OO

OR

+ +

+

( 93 - 96 )

( 97 - 98 )

BuLi THF-HMPA

-30 iexclaelig

99

Reduction

100

+

93 9495

96 97 98

O

OBnBnO

BnO

OO

O

OO

HO

O

O

OO

PPh3I-

O

OHHO

HO

O

HOOH OH

HO

OBnBnO

CHO

BnO

O

+

BuLi THF-HMPA

-30 oC

1 p-MeC 6H4SO2-

NH2NH2 AcONa

2 H2 Pd(OH)2 3 bar

3 Amberli te H+

+

10197

102

103





Scheme (22)

O

BnOOBn

BnO OTBDPS

PPh3I-

BnO

H

O

BnOOBn

OTBDPS

OO

O

OO

O

CHOO

O

OO

O

BnO

O

BnOOBn

BnO

OO

O

OO

H

HOBn

BnO OTBDPS

O

BnOOBn

BnO O

OO

O

OO

H

OBn

BnO OTBDPS

PPh3I-

O

BnO

O

BnOOBn

BnO OTBDPS

PPh3I-

O

AcOOAc

AcO

O

AcOOAc

AcO

OO

O

OO

O

AcOOAc

AcO OAc

O

BnOOBn

BnO

O

BnOOBn

BnO

OO

O

OO

H

H

O

BnOOBn

BnO OTBDPS

H

1 TBAF2 PCC

+107 36

+

1 TBAF2 PCC3

+


104

33

105

106104

104

108109

BuLi THF-HMPA

-50 o C

70EZ 19

BuLi THF-HMPA

-50 o C







Scheme (23)

Scheme (24)

BnOO

OBnCHO

OBn

O

OBn

PPh3I-

OBn

OBn

O

OBn

BnOBnO

O

OBnOBn

OBnH

O

OH

HOHO

O

OHOH

OH+

BuLi

THF-HMPA

-20 oC+

1 TBAF2 H2 Pd(OH)2C

112 65 113 100

110

111

O

OBnCHO

OBnBnO

O

OBn

BnOBnO

O

OBnCH(OiPr)2

OBnH

O

OBnCH(OiPr)2

PPh3I-

OBn

O

OBn

BnOBnO

O

OBn

OBnH

O

OBnOBn

BnOH

O

OH

HOHO

O

OH

OH

O

OHOH

HO

++

BuLi

THF-HMPA

-20 oC

BuLi

THF-HMPA

-20 oC

TFA H2 O THF rt

115 49

116 R = CH(OiPr)2

117 R = CHO

118 45

H2 Pd(OH)2C

110

114

114

119


Scheme (25)

Scheme (26)

OBn

R1

R2

PPh3BF4-O

O

OOHC

O

O

O

O

O

O

O

O

HO

O

O

O

O

O O

OBn

R1

R2

O

O

O

O

O

O

H

O

OBn

R1

R2

O

O

O

O

O

O

O

O

OBn

R1

R2

O

O

O

+

BCl3 (005 equiv)

MS 4A CH2 Cl2 0 o C

+



R1 R2 = OBn H

120a - b

121

122a - b

123a - b

124

125a - b

OTBDPS

BnO X

SO Ph

O

BnO

OHCO

BnO

OMeOBn

OBn

O

BnO

OTBDPS

BnO

SO Ph

O

BnO

OMeOBn

OBn

O

HO

OMeOH

OHO

HOHO

OH

OH

128

229 74

1 RaNi (74)

2 BH3 DMS

NaOH H 2O2 (74)

3 H2 PdC (70)

130 74

LDA THF

-100 oC

126 X = H

127 X = Li


Scheme (27)

Scheme (28)










O

BnO

OTBDPS

BnO X

SO Ph

O

BnO

OBn

BnO Li

SO Ph

DMF

OHO

HOOH

OH

O OH

OH

HO

OHOH

O

BnO

OTBDPS

BnO

SO Ph

O

OBn

OBnOBnSO

Ph

OH

131 X = Li

132 X = CHO

THF -100 oC

1 Ra-Ni

2 BH3 DMS NaOH H2O2

3 H2 PdC

131

133

134

OBnO

OBnOMe

BnO

Li

OBnO

BnOOBn

OBn

OOBn

OBnOMeBnO

OH

OBnO

BnOOBn

OBn

O

n-BuLi

BnO

OMe

BnO

BrBr

O

OBn

OHO

OH

OH

HO

OHO

OH

HO

OMe

O

BnO

OMeOBn

O

BnO

139 92

1BF3 OEt2 EtOH

2 H2 PdC AcOH

140 52 over 2 steps

135 136 137

138

CBr4 PPh3








Scheme (29)

O

BnO

BnOOBn

OBn

OOBn

OBnOMe

OBnOH

O

BnO

BnO

OBn

OBn

O

O

BnOOBn

OMe

BnO

Li

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnOBnO

OBn

OBnBnO

O

BnO

BnO

OBn

O

OBnO

OBn

OBnBnO

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OMe



1 BF3 OEt2 Et3 OH

2 H2 PtO2 EtOAc

145 76

1 H2 SO4 AcOH

2 PCC

146 62

repeat steps

repeat st eps

141 142

143

147

148


Scheme (30)

Scheme (31)

O

BnOOBn

OMe

Li

BnO

OPivBnO

OBn

OBn

BnO

O OO

BF3 OEt2

OBnO

OBn

OBn

BnO

OO

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

CAN

OBnO

OBn

OBn

BnO

OO

OO

BnOOBn

BnO

OMe

OHBnO

OBn

OBn

BnO

OHO

O

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

OPivBnO

OBn

OBn

BnO

OH OO

O

OMe

BnOOBn

BnO

OAcO

OAc

OAc

AcO

OAcOAc

OAcO

OAc

AcO

OMe

1

2 NaOMe MeOH


with a-isomer

1 Et3N Pyr H2O

2 H2 PdC H+

3 Ac2 O Pyr

149 151

152153

154 155

150

OBn

BnO

OBnO

OBn

BnO

OBnO

BnO

MeO

OBnO

OBn

BnO

O

OMe

AcO

OAcO

OAc

OAc

AcO

OAcO

OAc

O

BnOOBn

OMe

BnO

159 74 over 2 steps

+

BuLi ZnCl2 THF

1 H2 PdC2 Ac2O Pyr

156 157

158 59


Scheme (32)

Scheme (33)



OBnO

OBn

BnO

O

OBnO

ClZnO

OBn

BnOCl

R

OBnO

O

OBn

BnOCl

ZnR

O

ZnR

OBnO

OBn

BnO

160 161

162163

O

OBn

OBnBnO

O

O

OBn

OBnBnO H

TMS

O

OBn

OBnBnO H

O

OBn

BnO

OBnHO

O

OBn

OBnBnO OH

TMS

OBnBnO HO

OBn

TMS

O

OR

ORRO H

O

OR

RO

OR

OBn

OBnBnO

H

TMS

O+

K2CO3 MeOH

1 n-BuLi THF -78 oC

2 164

164165 66

166α 60 166β 13167 97


168 85

169 R = Bn 83


H2 (1 atm)Pd(OH) 2C

TMS-acetyl ene


-78 o C


O

OHCOBn

OBnBnO

OMe

O

CO2MeAcO

OAcAcHN

OAc

SO2

NAcO

OBnH

H

OBn

OBn

H

O

OMeH HH

A

O

CO2MeAcO

OAcAcHN

OAc

O

OBnOMe

OBnOBn

HO

AcO

+

Nu

174175

176

SmI2 THF

Scheme (34)

Scheme (35)

Scheme (36)

O

BnO

BnO

BnO

Si lylO

O2S N

O

BnO

HO R2R1

BnOBnO

SilylO

OBnO

BnO

BnO

SilylO

Sm(III)

R1COR2 SmI2 THF

171 172

173

NHBoc

OAcO

AcO

AcHN O

O

CO2BnO

OO

OO

OH

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

R2

O

CO2Me

AcHN

OAc

AcO

R1

AcO

AcO

AcHNO CO2Bn

NHBoc

AcO

OAc

O

Zn(BH4)2

180 R1 R2 = H OH ( RS 11)

181 R1 R2 = O

182 R1 = H R2 = OH de gt 90

DMSO Ac2O

177178

179

13 steps

22 equiv SmI2 THF


Scheme (37)

Fig (2)




4 CATIONIC METHODS


OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO


+

Ac2O Pyr

187 X = OMP

188 X = SPh 73



+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3















Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331



































































Scheme (17)

Scheme (18)

O

O O

O

O OH

O OMe

OBnBnO

SO2

P

EtO

EtO

O

OBn

O

OMe

OAc

OAc

OAcO

O O

O

O

O

OO OMe

OBnBnO

SO2

OBn

O

O O

O

O O

O

O

O

OMe

OBn

OBn

OBn

83 50 E only

80

+

NaH THF -78 oC

82 86αβ 11

KOHAl2O3

CBr2F2 CH2Cl2

tBuOH 5 oC

2 h

1 H2PdC EtOAc RT 7h

2 Ac2 O Pyr RT

84 69 over 2 st eps

81

O

O O

O

O OH POEt

OEt

O

SO2

P

EtO

EtOO

O

O

O

OO

O

O

O

O O

O

O

O O

O

O

O

O SO2

O

O

O

O

O

O O

O

OO

O

O

85 75βαββ ca 31

86 66β αββ = 141 E only

H2PdC EtOAc

87 76βαβ β = 141

21 NaH THF -78 o C

80 (2 equiv)











25 C-1 Vinyl Anions


Scheme (19)

OCH3

O O

OPhS

PhS

O O

OO

OCH3

O O

OO O

O H

OCH3

O O

OPhSPhS

O O

O OH

OCH3

O O

OO O

O OH

+

n-BuLi THF -78 oC


Et3SiH BF3 OEt2

90 77


-78 oC

88

89







Scheme (20)

Scheme (21)

OO O

O

O CHO

O

BnOOBn

BnO

OBn

CHO

OBn

CHO

BnO

O

BnOBnO

O

BnOOBn

BnO OBn

CHO

PPh3I-

OO

O

OO

O

OMeOBn

OBn

OBn

PPh3I-

OCHO

O

PPh3I-

ORRO

RO

OO

ORRHO

OO

OR

+ +

+

( 93 - 96 )

( 97 - 98 )

BuLi THF-HMPA

-30 iexclaelig

99

Reduction

100

+

93 9495

96 97 98

O

OBnBnO

BnO

OO

O

OO

HO

O

O

OO

PPh3I-

O

OHHO

HO

O

HOOH OH

HO

OBnBnO

CHO

BnO

O

+

BuLi THF-HMPA

-30 oC

1 p-MeC 6H4SO2-

NH2NH2 AcONa

2 H2 Pd(OH)2 3 bar

3 Amberli te H+

+

10197

102

103





Scheme (22)

O

BnOOBn

BnO OTBDPS

PPh3I-

BnO

H

O

BnOOBn

OTBDPS

OO

O

OO

O

CHOO

O

OO

O

BnO

O

BnOOBn

BnO

OO

O

OO

H

HOBn

BnO OTBDPS

O

BnOOBn

BnO O

OO

O

OO

H

OBn

BnO OTBDPS

PPh3I-

O

BnO

O

BnOOBn

BnO OTBDPS

PPh3I-

O

AcOOAc

AcO

O

AcOOAc

AcO

OO

O

OO

O

AcOOAc

AcO OAc

O

BnOOBn

BnO

O

BnOOBn

BnO

OO

O

OO

H

H

O

BnOOBn

BnO OTBDPS

H

1 TBAF2 PCC

+107 36

+

1 TBAF2 PCC3

+


104

33

105

106104

104

108109

BuLi THF-HMPA

-50 o C

70EZ 19

BuLi THF-HMPA

-50 o C







Scheme (23)

Scheme (24)

BnOO

OBnCHO

OBn

O

OBn

PPh3I-

OBn

OBn

O

OBn

BnOBnO

O

OBnOBn

OBnH

O

OH

HOHO

O

OHOH

OH+

BuLi

THF-HMPA

-20 oC+

1 TBAF2 H2 Pd(OH)2C

112 65 113 100

110

111

O

OBnCHO

OBnBnO

O

OBn

BnOBnO

O

OBnCH(OiPr)2

OBnH

O

OBnCH(OiPr)2

PPh3I-

OBn

O

OBn

BnOBnO

O

OBn

OBnH

O

OBnOBn

BnOH

O

OH

HOHO

O

OH

OH

O

OHOH

HO

++

BuLi

THF-HMPA

-20 oC

BuLi

THF-HMPA

-20 oC

TFA H2 O THF rt

115 49

116 R = CH(OiPr)2

117 R = CHO

118 45

H2 Pd(OH)2C

110

114

114

119


Scheme (25)

Scheme (26)

OBn

R1

R2

PPh3BF4-O

O

OOHC

O

O

O

O

O

O

O

O

HO

O

O

O

O

O O

OBn

R1

R2

O

O

O

O

O

O

H

O

OBn

R1

R2

O

O

O

O

O

O

O

O

OBn

R1

R2

O

O

O

+

BCl3 (005 equiv)

MS 4A CH2 Cl2 0 o C

+



R1 R2 = OBn H

120a - b

121

122a - b

123a - b

124

125a - b

OTBDPS

BnO X

SO Ph

O

BnO

OHCO

BnO

OMeOBn

OBn

O

BnO

OTBDPS

BnO

SO Ph

O

BnO

OMeOBn

OBn

O

HO

OMeOH

OHO

HOHO

OH

OH

128

229 74

1 RaNi (74)

2 BH3 DMS

NaOH H 2O2 (74)

3 H2 PdC (70)

130 74

LDA THF

-100 oC

126 X = H

127 X = Li


Scheme (27)

Scheme (28)










O

BnO

OTBDPS

BnO X

SO Ph

O

BnO

OBn

BnO Li

SO Ph

DMF

OHO

HOOH

OH

O OH

OH

HO

OHOH

O

BnO

OTBDPS

BnO

SO Ph

O

OBn

OBnOBnSO

Ph

OH

131 X = Li

132 X = CHO

THF -100 oC

1 Ra-Ni

2 BH3 DMS NaOH H2O2

3 H2 PdC

131

133

134

OBnO

OBnOMe

BnO

Li

OBnO

BnOOBn

OBn

OOBn

OBnOMeBnO

OH

OBnO

BnOOBn

OBn

O

n-BuLi

BnO

OMe

BnO

BrBr

O

OBn

OHO

OH

OH

HO

OHO

OH

HO

OMe

O

BnO

OMeOBn

O

BnO

139 92

1BF3 OEt2 EtOH

2 H2 PdC AcOH

140 52 over 2 steps

135 136 137

138

CBr4 PPh3








Scheme (29)

O

BnO

BnOOBn

OBn

OOBn

OBnOMe

OBnOH

O

BnO

BnO

OBn

OBn

O

O

BnOOBn

OMe

BnO

Li

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnOBnO

OBn

OBnBnO

O

BnO

BnO

OBn

O

OBnO

OBn

OBnBnO

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OMe



1 BF3 OEt2 Et3 OH

2 H2 PtO2 EtOAc

145 76

1 H2 SO4 AcOH

2 PCC

146 62

repeat steps

repeat st eps

141 142

143

147

148


Scheme (30)

Scheme (31)

O

BnOOBn

OMe

Li

BnO

OPivBnO

OBn

OBn

BnO

O OO

BF3 OEt2

OBnO

OBn

OBn

BnO

OO

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

CAN

OBnO

OBn

OBn

BnO

OO

OO

BnOOBn

BnO

OMe

OHBnO

OBn

OBn

BnO

OHO

O

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

OPivBnO

OBn

OBn

BnO

OH OO

O

OMe

BnOOBn

BnO

OAcO

OAc

OAc

AcO

OAcOAc

OAcO

OAc

AcO

OMe

1

2 NaOMe MeOH


with a-isomer

1 Et3N Pyr H2O

2 H2 PdC H+

3 Ac2 O Pyr

149 151

152153

154 155

150

OBn

BnO

OBnO

OBn

BnO

OBnO

BnO

MeO

OBnO

OBn

BnO

O

OMe

AcO

OAcO

OAc

OAc

AcO

OAcO

OAc

O

BnOOBn

OMe

BnO

159 74 over 2 steps

+

BuLi ZnCl2 THF

1 H2 PdC2 Ac2O Pyr

156 157

158 59


Scheme (32)

Scheme (33)



OBnO

OBn

BnO

O

OBnO

ClZnO

OBn

BnOCl

R

OBnO

O

OBn

BnOCl

ZnR

O

ZnR

OBnO

OBn

BnO

160 161

162163

O

OBn

OBnBnO

O

O

OBn

OBnBnO H

TMS

O

OBn

OBnBnO H

O

OBn

BnO

OBnHO

O

OBn

OBnBnO OH

TMS

OBnBnO HO

OBn

TMS

O

OR

ORRO H

O

OR

RO

OR

OBn

OBnBnO

H

TMS

O+

K2CO3 MeOH

1 n-BuLi THF -78 oC

2 164

164165 66

166α 60 166β 13167 97


168 85

169 R = Bn 83


H2 (1 atm)Pd(OH) 2C

TMS-acetyl ene


-78 o C


O

OHCOBn

OBnBnO

OMe

O

CO2MeAcO

OAcAcHN

OAc

SO2

NAcO

OBnH

H

OBn

OBn

H

O

OMeH HH

A

O

CO2MeAcO

OAcAcHN

OAc

O

OBnOMe

OBnOBn

HO

AcO

+

Nu

174175

176

SmI2 THF

Scheme (34)

Scheme (35)

Scheme (36)

O

BnO

BnO

BnO

Si lylO

O2S N

O

BnO

HO R2R1

BnOBnO

SilylO

OBnO

BnO

BnO

SilylO

Sm(III)

R1COR2 SmI2 THF

171 172

173

NHBoc

OAcO

AcO

AcHN O

O

CO2BnO

OO

OO

OH

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

R2

O

CO2Me

AcHN

OAc

AcO

R1

AcO

AcO

AcHNO CO2Bn

NHBoc

AcO

OAc

O

Zn(BH4)2

180 R1 R2 = H OH ( RS 11)

181 R1 R2 = O

182 R1 = H R2 = OH de gt 90

DMSO Ac2O

177178

179

13 steps

22 equiv SmI2 THF


Scheme (37)

Fig (2)




4 CATIONIC METHODS


OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO


+

Ac2O Pyr

187 X = OMP

188 X = SPh 73



+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3















Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331








































































25 C-1 Vinyl Anions


Scheme (19)

OCH3

O O

OPhS

PhS

O O

OO

OCH3

O O

OO O

O H

OCH3

O O

OPhSPhS

O O

O OH

OCH3

O O

OO O

O OH

+

n-BuLi THF -78 oC


Et3SiH BF3 OEt2

90 77


-78 oC

88

89







Scheme (20)

Scheme (21)

OO O

O

O CHO

O

BnOOBn

BnO

OBn

CHO

OBn

CHO

BnO

O

BnOBnO

O

BnOOBn

BnO OBn

CHO

PPh3I-

OO

O

OO

O

OMeOBn

OBn

OBn

PPh3I-

OCHO

O

PPh3I-

ORRO

RO

OO

ORRHO

OO

OR

+ +

+

( 93 - 96 )

( 97 - 98 )

BuLi THF-HMPA

-30 iexclaelig

99

Reduction

100

+

93 9495

96 97 98

O

OBnBnO

BnO

OO

O

OO

HO

O

O

OO

PPh3I-

O

OHHO

HO

O

HOOH OH

HO

OBnBnO

CHO

BnO

O

+

BuLi THF-HMPA

-30 oC

1 p-MeC 6H4SO2-

NH2NH2 AcONa

2 H2 Pd(OH)2 3 bar

3 Amberli te H+

+

10197

102

103





Scheme (22)

O

BnOOBn

BnO OTBDPS

PPh3I-

BnO

H

O

BnOOBn

OTBDPS

OO

O

OO

O

CHOO

O

OO

O

BnO

O

BnOOBn

BnO

OO

O

OO

H

HOBn

BnO OTBDPS

O

BnOOBn

BnO O

OO

O

OO

H

OBn

BnO OTBDPS

PPh3I-

O

BnO

O

BnOOBn

BnO OTBDPS

PPh3I-

O

AcOOAc

AcO

O

AcOOAc

AcO

OO

O

OO

O

AcOOAc

AcO OAc

O

BnOOBn

BnO

O

BnOOBn

BnO

OO

O

OO

H

H

O

BnOOBn

BnO OTBDPS

H

1 TBAF2 PCC

+107 36

+

1 TBAF2 PCC3

+


104

33

105

106104

104

108109

BuLi THF-HMPA

-50 o C

70EZ 19

BuLi THF-HMPA

-50 o C







Scheme (23)

Scheme (24)

BnOO

OBnCHO

OBn

O

OBn

PPh3I-

OBn

OBn

O

OBn

BnOBnO

O

OBnOBn

OBnH

O

OH

HOHO

O

OHOH

OH+

BuLi

THF-HMPA

-20 oC+

1 TBAF2 H2 Pd(OH)2C

112 65 113 100

110

111

O

OBnCHO

OBnBnO

O

OBn

BnOBnO

O

OBnCH(OiPr)2

OBnH

O

OBnCH(OiPr)2

PPh3I-

OBn

O

OBn

BnOBnO

O

OBn

OBnH

O

OBnOBn

BnOH

O

OH

HOHO

O

OH

OH

O

OHOH

HO

++

BuLi

THF-HMPA

-20 oC

BuLi

THF-HMPA

-20 oC

TFA H2 O THF rt

115 49

116 R = CH(OiPr)2

117 R = CHO

118 45

H2 Pd(OH)2C

110

114

114

119


Scheme (25)

Scheme (26)

OBn

R1

R2

PPh3BF4-O

O

OOHC

O

O

O

O

O

O

O

O

HO

O

O

O

O

O O

OBn

R1

R2

O

O

O

O

O

O

H

O

OBn

R1

R2

O

O

O

O

O

O

O

O

OBn

R1

R2

O

O

O

+

BCl3 (005 equiv)

MS 4A CH2 Cl2 0 o C

+



R1 R2 = OBn H

120a - b

121

122a - b

123a - b

124

125a - b

OTBDPS

BnO X

SO Ph

O

BnO

OHCO

BnO

OMeOBn

OBn

O

BnO

OTBDPS

BnO

SO Ph

O

BnO

OMeOBn

OBn

O

HO

OMeOH

OHO

HOHO

OH

OH

128

229 74

1 RaNi (74)

2 BH3 DMS

NaOH H 2O2 (74)

3 H2 PdC (70)

130 74

LDA THF

-100 oC

126 X = H

127 X = Li


Scheme (27)

Scheme (28)










O

BnO

OTBDPS

BnO X

SO Ph

O

BnO

OBn

BnO Li

SO Ph

DMF

OHO

HOOH

OH

O OH

OH

HO

OHOH

O

BnO

OTBDPS

BnO

SO Ph

O

OBn

OBnOBnSO

Ph

OH

131 X = Li

132 X = CHO

THF -100 oC

1 Ra-Ni

2 BH3 DMS NaOH H2O2

3 H2 PdC

131

133

134

OBnO

OBnOMe

BnO

Li

OBnO

BnOOBn

OBn

OOBn

OBnOMeBnO

OH

OBnO

BnOOBn

OBn

O

n-BuLi

BnO

OMe

BnO

BrBr

O

OBn

OHO

OH

OH

HO

OHO

OH

HO

OMe

O

BnO

OMeOBn

O

BnO

139 92

1BF3 OEt2 EtOH

2 H2 PdC AcOH

140 52 over 2 steps

135 136 137

138

CBr4 PPh3








Scheme (29)

O

BnO

BnOOBn

OBn

OOBn

OBnOMe

OBnOH

O

BnO

BnO

OBn

OBn

O

O

BnOOBn

OMe

BnO

Li

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnOBnO

OBn

OBnBnO

O

BnO

BnO

OBn

O

OBnO

OBn

OBnBnO

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OMe



1 BF3 OEt2 Et3 OH

2 H2 PtO2 EtOAc

145 76

1 H2 SO4 AcOH

2 PCC

146 62

repeat steps

repeat st eps

141 142

143

147

148


Scheme (30)

Scheme (31)

O

BnOOBn

OMe

Li

BnO

OPivBnO

OBn

OBn

BnO

O OO

BF3 OEt2

OBnO

OBn

OBn

BnO

OO

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

CAN

OBnO

OBn

OBn

BnO

OO

OO

BnOOBn

BnO

OMe

OHBnO

OBn

OBn

BnO

OHO

O

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

OPivBnO

OBn

OBn

BnO

OH OO

O

OMe

BnOOBn

BnO

OAcO

OAc

OAc

AcO

OAcOAc

OAcO

OAc

AcO

OMe

1

2 NaOMe MeOH


with a-isomer

1 Et3N Pyr H2O

2 H2 PdC H+

3 Ac2 O Pyr

149 151

152153

154 155

150

OBn

BnO

OBnO

OBn

BnO

OBnO

BnO

MeO

OBnO

OBn

BnO

O

OMe

AcO

OAcO

OAc

OAc

AcO

OAcO

OAc

O

BnOOBn

OMe

BnO

159 74 over 2 steps

+

BuLi ZnCl2 THF

1 H2 PdC2 Ac2O Pyr

156 157

158 59


Scheme (32)

Scheme (33)



OBnO

OBn

BnO

O

OBnO

ClZnO

OBn

BnOCl

R

OBnO

O

OBn

BnOCl

ZnR

O

ZnR

OBnO

OBn

BnO

160 161

162163

O

OBn

OBnBnO

O

O

OBn

OBnBnO H

TMS

O

OBn

OBnBnO H

O

OBn

BnO

OBnHO

O

OBn

OBnBnO OH

TMS

OBnBnO HO

OBn

TMS

O

OR

ORRO H

O

OR

RO

OR

OBn

OBnBnO

H

TMS

O+

K2CO3 MeOH

1 n-BuLi THF -78 oC

2 164

164165 66

166α 60 166β 13167 97


168 85

169 R = Bn 83


H2 (1 atm)Pd(OH) 2C

TMS-acetyl ene


-78 o C


O

OHCOBn

OBnBnO

OMe

O

CO2MeAcO

OAcAcHN

OAc

SO2

NAcO

OBnH

H

OBn

OBn

H

O

OMeH HH

A

O

CO2MeAcO

OAcAcHN

OAc

O

OBnOMe

OBnOBn

HO

AcO

+

Nu

174175

176

SmI2 THF

Scheme (34)

Scheme (35)

Scheme (36)

O

BnO

BnO

BnO

Si lylO

O2S N

O

BnO

HO R2R1

BnOBnO

SilylO

OBnO

BnO

BnO

SilylO

Sm(III)

R1COR2 SmI2 THF

171 172

173

NHBoc

OAcO

AcO

AcHN O

O

CO2BnO

OO

OO

OH

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

R2

O

CO2Me

AcHN

OAc

AcO

R1

AcO

AcO

AcHNO CO2Bn

NHBoc

AcO

OAc

O

Zn(BH4)2

180 R1 R2 = H OH ( RS 11)

181 R1 R2 = O

182 R1 = H R2 = OH de gt 90

DMSO Ac2O

177178

179

13 steps

22 equiv SmI2 THF


Scheme (37)

Fig (2)




4 CATIONIC METHODS


OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO


+

Ac2O Pyr

187 X = OMP

188 X = SPh 73



+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3















Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331






































































Scheme (20)

Scheme (21)

OO O

O

O CHO

O

BnOOBn

BnO

OBn

CHO

OBn

CHO

BnO

O

BnOBnO

O

BnOOBn

BnO OBn

CHO

PPh3I-

OO

O

OO

O

OMeOBn

OBn

OBn

PPh3I-

OCHO

O

PPh3I-

ORRO

RO

OO

ORRHO

OO

OR

+ +

+

( 93 - 96 )

( 97 - 98 )

BuLi THF-HMPA

-30 iexclaelig

99

Reduction

100

+

93 9495

96 97 98

O

OBnBnO

BnO

OO

O

OO

HO

O

O

OO

PPh3I-

O

OHHO

HO

O

HOOH OH

HO

OBnBnO

CHO

BnO

O

+

BuLi THF-HMPA

-30 oC

1 p-MeC 6H4SO2-

NH2NH2 AcONa

2 H2 Pd(OH)2 3 bar

3 Amberli te H+

+

10197

102

103





Scheme (22)

O

BnOOBn

BnO OTBDPS

PPh3I-

BnO

H

O

BnOOBn

OTBDPS

OO

O

OO

O

CHOO

O

OO

O

BnO

O

BnOOBn

BnO

OO

O

OO

H

HOBn

BnO OTBDPS

O

BnOOBn

BnO O

OO

O

OO

H

OBn

BnO OTBDPS

PPh3I-

O

BnO

O

BnOOBn

BnO OTBDPS

PPh3I-

O

AcOOAc

AcO

O

AcOOAc

AcO

OO

O

OO

O

AcOOAc

AcO OAc

O

BnOOBn

BnO

O

BnOOBn

BnO

OO

O

OO

H

H

O

BnOOBn

BnO OTBDPS

H

1 TBAF2 PCC

+107 36

+

1 TBAF2 PCC3

+


104

33

105

106104

104

108109

BuLi THF-HMPA

-50 o C

70EZ 19

BuLi THF-HMPA

-50 o C







Scheme (23)

Scheme (24)

BnOO

OBnCHO

OBn

O

OBn

PPh3I-

OBn

OBn

O

OBn

BnOBnO

O

OBnOBn

OBnH

O

OH

HOHO

O

OHOH

OH+

BuLi

THF-HMPA

-20 oC+

1 TBAF2 H2 Pd(OH)2C

112 65 113 100

110

111

O

OBnCHO

OBnBnO

O

OBn

BnOBnO

O

OBnCH(OiPr)2

OBnH

O

OBnCH(OiPr)2

PPh3I-

OBn

O

OBn

BnOBnO

O

OBn

OBnH

O

OBnOBn

BnOH

O

OH

HOHO

O

OH

OH

O

OHOH

HO

++

BuLi

THF-HMPA

-20 oC

BuLi

THF-HMPA

-20 oC

TFA H2 O THF rt

115 49

116 R = CH(OiPr)2

117 R = CHO

118 45

H2 Pd(OH)2C

110

114

114

119


Scheme (25)

Scheme (26)

OBn

R1

R2

PPh3BF4-O

O

OOHC

O

O

O

O

O

O

O

O

HO

O

O

O

O

O O

OBn

R1

R2

O

O

O

O

O

O

H

O

OBn

R1

R2

O

O

O

O

O

O

O

O

OBn

R1

R2

O

O

O

+

BCl3 (005 equiv)

MS 4A CH2 Cl2 0 o C

+



R1 R2 = OBn H

120a - b

121

122a - b

123a - b

124

125a - b

OTBDPS

BnO X

SO Ph

O

BnO

OHCO

BnO

OMeOBn

OBn

O

BnO

OTBDPS

BnO

SO Ph

O

BnO

OMeOBn

OBn

O

HO

OMeOH

OHO

HOHO

OH

OH

128

229 74

1 RaNi (74)

2 BH3 DMS

NaOH H 2O2 (74)

3 H2 PdC (70)

130 74

LDA THF

-100 oC

126 X = H

127 X = Li


Scheme (27)

Scheme (28)










O

BnO

OTBDPS

BnO X

SO Ph

O

BnO

OBn

BnO Li

SO Ph

DMF

OHO

HOOH

OH

O OH

OH

HO

OHOH

O

BnO

OTBDPS

BnO

SO Ph

O

OBn

OBnOBnSO

Ph

OH

131 X = Li

132 X = CHO

THF -100 oC

1 Ra-Ni

2 BH3 DMS NaOH H2O2

3 H2 PdC

131

133

134

OBnO

OBnOMe

BnO

Li

OBnO

BnOOBn

OBn

OOBn

OBnOMeBnO

OH

OBnO

BnOOBn

OBn

O

n-BuLi

BnO

OMe

BnO

BrBr

O

OBn

OHO

OH

OH

HO

OHO

OH

HO

OMe

O

BnO

OMeOBn

O

BnO

139 92

1BF3 OEt2 EtOH

2 H2 PdC AcOH

140 52 over 2 steps

135 136 137

138

CBr4 PPh3








Scheme (29)

O

BnO

BnOOBn

OBn

OOBn

OBnOMe

OBnOH

O

BnO

BnO

OBn

OBn

O

O

BnOOBn

OMe

BnO

Li

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnOBnO

OBn

OBnBnO

O

BnO

BnO

OBn

O

OBnO

OBn

OBnBnO

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OMe



1 BF3 OEt2 Et3 OH

2 H2 PtO2 EtOAc

145 76

1 H2 SO4 AcOH

2 PCC

146 62

repeat steps

repeat st eps

141 142

143

147

148


Scheme (30)

Scheme (31)

O

BnOOBn

OMe

Li

BnO

OPivBnO

OBn

OBn

BnO

O OO

BF3 OEt2

OBnO

OBn

OBn

BnO

OO

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

CAN

OBnO

OBn

OBn

BnO

OO

OO

BnOOBn

BnO

OMe

OHBnO

OBn

OBn

BnO

OHO

O

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

OPivBnO

OBn

OBn

BnO

OH OO

O

OMe

BnOOBn

BnO

OAcO

OAc

OAc

AcO

OAcOAc

OAcO

OAc

AcO

OMe

1

2 NaOMe MeOH


with a-isomer

1 Et3N Pyr H2O

2 H2 PdC H+

3 Ac2 O Pyr

149 151

152153

154 155

150

OBn

BnO

OBnO

OBn

BnO

OBnO

BnO

MeO

OBnO

OBn

BnO

O

OMe

AcO

OAcO

OAc

OAc

AcO

OAcO

OAc

O

BnOOBn

OMe

BnO

159 74 over 2 steps

+

BuLi ZnCl2 THF

1 H2 PdC2 Ac2O Pyr

156 157

158 59


Scheme (32)

Scheme (33)



OBnO

OBn

BnO

O

OBnO

ClZnO

OBn

BnOCl

R

OBnO

O

OBn

BnOCl

ZnR

O

ZnR

OBnO

OBn

BnO

160 161

162163

O

OBn

OBnBnO

O

O

OBn

OBnBnO H

TMS

O

OBn

OBnBnO H

O

OBn

BnO

OBnHO

O

OBn

OBnBnO OH

TMS

OBnBnO HO

OBn

TMS

O

OR

ORRO H

O

OR

RO

OR

OBn

OBnBnO

H

TMS

O+

K2CO3 MeOH

1 n-BuLi THF -78 oC

2 164

164165 66

166α 60 166β 13167 97


168 85

169 R = Bn 83


H2 (1 atm)Pd(OH) 2C

TMS-acetyl ene


-78 o C


O

OHCOBn

OBnBnO

OMe

O

CO2MeAcO

OAcAcHN

OAc

SO2

NAcO

OBnH

H

OBn

OBn

H

O

OMeH HH

A

O

CO2MeAcO

OAcAcHN

OAc

O

OBnOMe

OBnOBn

HO

AcO

+

Nu

174175

176

SmI2 THF

Scheme (34)

Scheme (35)

Scheme (36)

O

BnO

BnO

BnO

Si lylO

O2S N

O

BnO

HO R2R1

BnOBnO

SilylO

OBnO

BnO

BnO

SilylO

Sm(III)

R1COR2 SmI2 THF

171 172

173

NHBoc

OAcO

AcO

AcHN O

O

CO2BnO

OO

OO

OH

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

R2

O

CO2Me

AcHN

OAc

AcO

R1

AcO

AcO

AcHNO CO2Bn

NHBoc

AcO

OAc

O

Zn(BH4)2

180 R1 R2 = H OH ( RS 11)

181 R1 R2 = O

182 R1 = H R2 = OH de gt 90

DMSO Ac2O

177178

179

13 steps

22 equiv SmI2 THF


Scheme (37)

Fig (2)




4 CATIONIC METHODS


OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO


+

Ac2O Pyr

187 X = OMP

188 X = SPh 73



+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3















Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331




































































Scheme (22)

O

BnOOBn

BnO OTBDPS

PPh3I-

BnO

H

O

BnOOBn

OTBDPS

OO

O

OO

O

CHOO

O

OO

O

BnO

O

BnOOBn

BnO

OO

O

OO

H

HOBn

BnO OTBDPS

O

BnOOBn

BnO O

OO

O

OO

H

OBn

BnO OTBDPS

PPh3I-

O

BnO

O

BnOOBn

BnO OTBDPS

PPh3I-

O

AcOOAc

AcO

O

AcOOAc

AcO

OO

O

OO

O

AcOOAc

AcO OAc

O

BnOOBn

BnO

O

BnOOBn

BnO

OO

O

OO

H

H

O

BnOOBn

BnO OTBDPS

H

1 TBAF2 PCC

+107 36

+

1 TBAF2 PCC3

+


104

33

105

106104

104

108109

BuLi THF-HMPA

-50 o C

70EZ 19

BuLi THF-HMPA

-50 o C







Scheme (23)

Scheme (24)

BnOO

OBnCHO

OBn

O

OBn

PPh3I-

OBn

OBn

O

OBn

BnOBnO

O

OBnOBn

OBnH

O

OH

HOHO

O

OHOH

OH+

BuLi

THF-HMPA

-20 oC+

1 TBAF2 H2 Pd(OH)2C

112 65 113 100

110

111

O

OBnCHO

OBnBnO

O

OBn

BnOBnO

O

OBnCH(OiPr)2

OBnH

O

OBnCH(OiPr)2

PPh3I-

OBn

O

OBn

BnOBnO

O

OBn

OBnH

O

OBnOBn

BnOH

O

OH

HOHO

O

OH

OH

O

OHOH

HO

++

BuLi

THF-HMPA

-20 oC

BuLi

THF-HMPA

-20 oC

TFA H2 O THF rt

115 49

116 R = CH(OiPr)2

117 R = CHO

118 45

H2 Pd(OH)2C

110

114

114

119


Scheme (25)

Scheme (26)

OBn

R1

R2

PPh3BF4-O

O

OOHC

O

O

O

O

O

O

O

O

HO

O

O

O

O

O O

OBn

R1

R2

O

O

O

O

O

O

H

O

OBn

R1

R2

O

O

O

O

O

O

O

O

OBn

R1

R2

O

O

O

+

BCl3 (005 equiv)

MS 4A CH2 Cl2 0 o C

+



R1 R2 = OBn H

120a - b

121

122a - b

123a - b

124

125a - b

OTBDPS

BnO X

SO Ph

O

BnO

OHCO

BnO

OMeOBn

OBn

O

BnO

OTBDPS

BnO

SO Ph

O

BnO

OMeOBn

OBn

O

HO

OMeOH

OHO

HOHO

OH

OH

128

229 74

1 RaNi (74)

2 BH3 DMS

NaOH H 2O2 (74)

3 H2 PdC (70)

130 74

LDA THF

-100 oC

126 X = H

127 X = Li


Scheme (27)

Scheme (28)










O

BnO

OTBDPS

BnO X

SO Ph

O

BnO

OBn

BnO Li

SO Ph

DMF

OHO

HOOH

OH

O OH

OH

HO

OHOH

O

BnO

OTBDPS

BnO

SO Ph

O

OBn

OBnOBnSO

Ph

OH

131 X = Li

132 X = CHO

THF -100 oC

1 Ra-Ni

2 BH3 DMS NaOH H2O2

3 H2 PdC

131

133

134

OBnO

OBnOMe

BnO

Li

OBnO

BnOOBn

OBn

OOBn

OBnOMeBnO

OH

OBnO

BnOOBn

OBn

O

n-BuLi

BnO

OMe

BnO

BrBr

O

OBn

OHO

OH

OH

HO

OHO

OH

HO

OMe

O

BnO

OMeOBn

O

BnO

139 92

1BF3 OEt2 EtOH

2 H2 PdC AcOH

140 52 over 2 steps

135 136 137

138

CBr4 PPh3








Scheme (29)

O

BnO

BnOOBn

OBn

OOBn

OBnOMe

OBnOH

O

BnO

BnO

OBn

OBn

O

O

BnOOBn

OMe

BnO

Li

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnOBnO

OBn

OBnBnO

O

BnO

BnO

OBn

O

OBnO

OBn

OBnBnO

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OMe



1 BF3 OEt2 Et3 OH

2 H2 PtO2 EtOAc

145 76

1 H2 SO4 AcOH

2 PCC

146 62

repeat steps

repeat st eps

141 142

143

147

148


Scheme (30)

Scheme (31)

O

BnOOBn

OMe

Li

BnO

OPivBnO

OBn

OBn

BnO

O OO

BF3 OEt2

OBnO

OBn

OBn

BnO

OO

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

CAN

OBnO

OBn

OBn

BnO

OO

OO

BnOOBn

BnO

OMe

OHBnO

OBn

OBn

BnO

OHO

O

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

OPivBnO

OBn

OBn

BnO

OH OO

O

OMe

BnOOBn

BnO

OAcO

OAc

OAc

AcO

OAcOAc

OAcO

OAc

AcO

OMe

1

2 NaOMe MeOH


with a-isomer

1 Et3N Pyr H2O

2 H2 PdC H+

3 Ac2 O Pyr

149 151

152153

154 155

150

OBn

BnO

OBnO

OBn

BnO

OBnO

BnO

MeO

OBnO

OBn

BnO

O

OMe

AcO

OAcO

OAc

OAc

AcO

OAcO

OAc

O

BnOOBn

OMe

BnO

159 74 over 2 steps

+

BuLi ZnCl2 THF

1 H2 PdC2 Ac2O Pyr

156 157

158 59


Scheme (32)

Scheme (33)



OBnO

OBn

BnO

O

OBnO

ClZnO

OBn

BnOCl

R

OBnO

O

OBn

BnOCl

ZnR

O

ZnR

OBnO

OBn

BnO

160 161

162163

O

OBn

OBnBnO

O

O

OBn

OBnBnO H

TMS

O

OBn

OBnBnO H

O

OBn

BnO

OBnHO

O

OBn

OBnBnO OH

TMS

OBnBnO HO

OBn

TMS

O

OR

ORRO H

O

OR

RO

OR

OBn

OBnBnO

H

TMS

O+

K2CO3 MeOH

1 n-BuLi THF -78 oC

2 164

164165 66

166α 60 166β 13167 97


168 85

169 R = Bn 83


H2 (1 atm)Pd(OH) 2C

TMS-acetyl ene


-78 o C


O

OHCOBn

OBnBnO

OMe

O

CO2MeAcO

OAcAcHN

OAc

SO2

NAcO

OBnH

H

OBn

OBn

H

O

OMeH HH

A

O

CO2MeAcO

OAcAcHN

OAc

O

OBnOMe

OBnOBn

HO

AcO

+

Nu

174175

176

SmI2 THF

Scheme (34)

Scheme (35)

Scheme (36)

O

BnO

BnO

BnO

Si lylO

O2S N

O

BnO

HO R2R1

BnOBnO

SilylO

OBnO

BnO

BnO

SilylO

Sm(III)

R1COR2 SmI2 THF

171 172

173

NHBoc

OAcO

AcO

AcHN O

O

CO2BnO

OO

OO

OH

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

R2

O

CO2Me

AcHN

OAc

AcO

R1

AcO

AcO

AcHNO CO2Bn

NHBoc

AcO

OAc

O

Zn(BH4)2

180 R1 R2 = H OH ( RS 11)

181 R1 R2 = O

182 R1 = H R2 = OH de gt 90

DMSO Ac2O

177178

179

13 steps

22 equiv SmI2 THF


Scheme (37)

Fig (2)




4 CATIONIC METHODS


OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO


+

Ac2O Pyr

187 X = OMP

188 X = SPh 73



+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3















Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331






































































Scheme (23)

Scheme (24)

BnOO

OBnCHO

OBn

O

OBn

PPh3I-

OBn

OBn

O

OBn

BnOBnO

O

OBnOBn

OBnH

O

OH

HOHO

O

OHOH

OH+

BuLi

THF-HMPA

-20 oC+

1 TBAF2 H2 Pd(OH)2C

112 65 113 100

110

111

O

OBnCHO

OBnBnO

O

OBn

BnOBnO

O

OBnCH(OiPr)2

OBnH

O

OBnCH(OiPr)2

PPh3I-

OBn

O

OBn

BnOBnO

O

OBn

OBnH

O

OBnOBn

BnOH

O

OH

HOHO

O

OH

OH

O

OHOH

HO

++

BuLi

THF-HMPA

-20 oC

BuLi

THF-HMPA

-20 oC

TFA H2 O THF rt

115 49

116 R = CH(OiPr)2

117 R = CHO

118 45

H2 Pd(OH)2C

110

114

114

119


Scheme (25)

Scheme (26)

OBn

R1

R2

PPh3BF4-O

O

OOHC

O

O

O

O

O

O

O

O

HO

O

O

O

O

O O

OBn

R1

R2

O

O

O

O

O

O

H

O

OBn

R1

R2

O

O

O

O

O

O

O

O

OBn

R1

R2

O

O

O

+

BCl3 (005 equiv)

MS 4A CH2 Cl2 0 o C

+



R1 R2 = OBn H

120a - b

121

122a - b

123a - b

124

125a - b

OTBDPS

BnO X

SO Ph

O

BnO

OHCO

BnO

OMeOBn

OBn

O

BnO

OTBDPS

BnO

SO Ph

O

BnO

OMeOBn

OBn

O

HO

OMeOH

OHO

HOHO

OH

OH

128

229 74

1 RaNi (74)

2 BH3 DMS

NaOH H 2O2 (74)

3 H2 PdC (70)

130 74

LDA THF

-100 oC

126 X = H

127 X = Li


Scheme (27)

Scheme (28)










O

BnO

OTBDPS

BnO X

SO Ph

O

BnO

OBn

BnO Li

SO Ph

DMF

OHO

HOOH

OH

O OH

OH

HO

OHOH

O

BnO

OTBDPS

BnO

SO Ph

O

OBn

OBnOBnSO

Ph

OH

131 X = Li

132 X = CHO

THF -100 oC

1 Ra-Ni

2 BH3 DMS NaOH H2O2

3 H2 PdC

131

133

134

OBnO

OBnOMe

BnO

Li

OBnO

BnOOBn

OBn

OOBn

OBnOMeBnO

OH

OBnO

BnOOBn

OBn

O

n-BuLi

BnO

OMe

BnO

BrBr

O

OBn

OHO

OH

OH

HO

OHO

OH

HO

OMe

O

BnO

OMeOBn

O

BnO

139 92

1BF3 OEt2 EtOH

2 H2 PdC AcOH

140 52 over 2 steps

135 136 137

138

CBr4 PPh3








Scheme (29)

O

BnO

BnOOBn

OBn

OOBn

OBnOMe

OBnOH

O

BnO

BnO

OBn

OBn

O

O

BnOOBn

OMe

BnO

Li

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnOBnO

OBn

OBnBnO

O

BnO

BnO

OBn

O

OBnO

OBn

OBnBnO

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OMe



1 BF3 OEt2 Et3 OH

2 H2 PtO2 EtOAc

145 76

1 H2 SO4 AcOH

2 PCC

146 62

repeat steps

repeat st eps

141 142

143

147

148


Scheme (30)

Scheme (31)

O

BnOOBn

OMe

Li

BnO

OPivBnO

OBn

OBn

BnO

O OO

BF3 OEt2

OBnO

OBn

OBn

BnO

OO

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

CAN

OBnO

OBn

OBn

BnO

OO

OO

BnOOBn

BnO

OMe

OHBnO

OBn

OBn

BnO

OHO

O

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

OPivBnO

OBn

OBn

BnO

OH OO

O

OMe

BnOOBn

BnO

OAcO

OAc

OAc

AcO

OAcOAc

OAcO

OAc

AcO

OMe

1

2 NaOMe MeOH


with a-isomer

1 Et3N Pyr H2O

2 H2 PdC H+

3 Ac2 O Pyr

149 151

152153

154 155

150

OBn

BnO

OBnO

OBn

BnO

OBnO

BnO

MeO

OBnO

OBn

BnO

O

OMe

AcO

OAcO

OAc

OAc

AcO

OAcO

OAc

O

BnOOBn

OMe

BnO

159 74 over 2 steps

+

BuLi ZnCl2 THF

1 H2 PdC2 Ac2O Pyr

156 157

158 59


Scheme (32)

Scheme (33)



OBnO

OBn

BnO

O

OBnO

ClZnO

OBn

BnOCl

R

OBnO

O

OBn

BnOCl

ZnR

O

ZnR

OBnO

OBn

BnO

160 161

162163

O

OBn

OBnBnO

O

O

OBn

OBnBnO H

TMS

O

OBn

OBnBnO H

O

OBn

BnO

OBnHO

O

OBn

OBnBnO OH

TMS

OBnBnO HO

OBn

TMS

O

OR

ORRO H

O

OR

RO

OR

OBn

OBnBnO

H

TMS

O+

K2CO3 MeOH

1 n-BuLi THF -78 oC

2 164

164165 66

166α 60 166β 13167 97


168 85

169 R = Bn 83


H2 (1 atm)Pd(OH) 2C

TMS-acetyl ene


-78 o C


O

OHCOBn

OBnBnO

OMe

O

CO2MeAcO

OAcAcHN

OAc

SO2

NAcO

OBnH

H

OBn

OBn

H

O

OMeH HH

A

O

CO2MeAcO

OAcAcHN

OAc

O

OBnOMe

OBnOBn

HO

AcO

+

Nu

174175

176

SmI2 THF

Scheme (34)

Scheme (35)

Scheme (36)

O

BnO

BnO

BnO

Si lylO

O2S N

O

BnO

HO R2R1

BnOBnO

SilylO

OBnO

BnO

BnO

SilylO

Sm(III)

R1COR2 SmI2 THF

171 172

173

NHBoc

OAcO

AcO

AcHN O

O

CO2BnO

OO

OO

OH

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

R2

O

CO2Me

AcHN

OAc

AcO

R1

AcO

AcO

AcHNO CO2Bn

NHBoc

AcO

OAc

O

Zn(BH4)2

180 R1 R2 = H OH ( RS 11)

181 R1 R2 = O

182 R1 = H R2 = OH de gt 90

DMSO Ac2O

177178

179

13 steps

22 equiv SmI2 THF


Scheme (37)

Fig (2)




4 CATIONIC METHODS


OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO


+

Ac2O Pyr

187 X = OMP

188 X = SPh 73



+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3















Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331

































































Scheme (25)

Scheme (26)

OBn

R1

R2

PPh3BF4-O

O

OOHC

O

O

O

O

O

O

O

O

HO

O

O

O

O

O O

OBn

R1

R2

O

O

O

O

O

O

H

O

OBn

R1

R2

O

O

O

O

O

O

O

O

OBn

R1

R2

O

O

O

+

BCl3 (005 equiv)

MS 4A CH2 Cl2 0 o C

+



R1 R2 = OBn H

120a - b

121

122a - b

123a - b

124

125a - b

OTBDPS

BnO X

SO Ph

O

BnO

OHCO

BnO

OMeOBn

OBn

O

BnO

OTBDPS

BnO

SO Ph

O

BnO

OMeOBn

OBn

O

HO

OMeOH

OHO

HOHO

OH

OH

128

229 74

1 RaNi (74)

2 BH3 DMS

NaOH H 2O2 (74)

3 H2 PdC (70)

130 74

LDA THF

-100 oC

126 X = H

127 X = Li


Scheme (27)

Scheme (28)










O

BnO

OTBDPS

BnO X

SO Ph

O

BnO

OBn

BnO Li

SO Ph

DMF

OHO

HOOH

OH

O OH

OH

HO

OHOH

O

BnO

OTBDPS

BnO

SO Ph

O

OBn

OBnOBnSO

Ph

OH

131 X = Li

132 X = CHO

THF -100 oC

1 Ra-Ni

2 BH3 DMS NaOH H2O2

3 H2 PdC

131

133

134

OBnO

OBnOMe

BnO

Li

OBnO

BnOOBn

OBn

OOBn

OBnOMeBnO

OH

OBnO

BnOOBn

OBn

O

n-BuLi

BnO

OMe

BnO

BrBr

O

OBn

OHO

OH

OH

HO

OHO

OH

HO

OMe

O

BnO

OMeOBn

O

BnO

139 92

1BF3 OEt2 EtOH

2 H2 PdC AcOH

140 52 over 2 steps

135 136 137

138

CBr4 PPh3








Scheme (29)

O

BnO

BnOOBn

OBn

OOBn

OBnOMe

OBnOH

O

BnO

BnO

OBn

OBn

O

O

BnOOBn

OMe

BnO

Li

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnOBnO

OBn

OBnBnO

O

BnO

BnO

OBn

O

OBnO

OBn

OBnBnO

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OMe



1 BF3 OEt2 Et3 OH

2 H2 PtO2 EtOAc

145 76

1 H2 SO4 AcOH

2 PCC

146 62

repeat steps

repeat st eps

141 142

143

147

148


Scheme (30)

Scheme (31)

O

BnOOBn

OMe

Li

BnO

OPivBnO

OBn

OBn

BnO

O OO

BF3 OEt2

OBnO

OBn

OBn

BnO

OO

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

CAN

OBnO

OBn

OBn

BnO

OO

OO

BnOOBn

BnO

OMe

OHBnO

OBn

OBn

BnO

OHO

O

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

OPivBnO

OBn

OBn

BnO

OH OO

O

OMe

BnOOBn

BnO

OAcO

OAc

OAc

AcO

OAcOAc

OAcO

OAc

AcO

OMe

1

2 NaOMe MeOH


with a-isomer

1 Et3N Pyr H2O

2 H2 PdC H+

3 Ac2 O Pyr

149 151

152153

154 155

150

OBn

BnO

OBnO

OBn

BnO

OBnO

BnO

MeO

OBnO

OBn

BnO

O

OMe

AcO

OAcO

OAc

OAc

AcO

OAcO

OAc

O

BnOOBn

OMe

BnO

159 74 over 2 steps

+

BuLi ZnCl2 THF

1 H2 PdC2 Ac2O Pyr

156 157

158 59


Scheme (32)

Scheme (33)



OBnO

OBn

BnO

O

OBnO

ClZnO

OBn

BnOCl

R

OBnO

O

OBn

BnOCl

ZnR

O

ZnR

OBnO

OBn

BnO

160 161

162163

O

OBn

OBnBnO

O

O

OBn

OBnBnO H

TMS

O

OBn

OBnBnO H

O

OBn

BnO

OBnHO

O

OBn

OBnBnO OH

TMS

OBnBnO HO

OBn

TMS

O

OR

ORRO H

O

OR

RO

OR

OBn

OBnBnO

H

TMS

O+

K2CO3 MeOH

1 n-BuLi THF -78 oC

2 164

164165 66

166α 60 166β 13167 97


168 85

169 R = Bn 83


H2 (1 atm)Pd(OH) 2C

TMS-acetyl ene


-78 o C


O

OHCOBn

OBnBnO

OMe

O

CO2MeAcO

OAcAcHN

OAc

SO2

NAcO

OBnH

H

OBn

OBn

H

O

OMeH HH

A

O

CO2MeAcO

OAcAcHN

OAc

O

OBnOMe

OBnOBn

HO

AcO

+

Nu

174175

176

SmI2 THF

Scheme (34)

Scheme (35)

Scheme (36)

O

BnO

BnO

BnO

Si lylO

O2S N

O

BnO

HO R2R1

BnOBnO

SilylO

OBnO

BnO

BnO

SilylO

Sm(III)

R1COR2 SmI2 THF

171 172

173

NHBoc

OAcO

AcO

AcHN O

O

CO2BnO

OO

OO

OH

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

R2

O

CO2Me

AcHN

OAc

AcO

R1

AcO

AcO

AcHNO CO2Bn

NHBoc

AcO

OAc

O

Zn(BH4)2

180 R1 R2 = H OH ( RS 11)

181 R1 R2 = O

182 R1 = H R2 = OH de gt 90

DMSO Ac2O

177178

179

13 steps

22 equiv SmI2 THF


Scheme (37)

Fig (2)




4 CATIONIC METHODS


OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO


+

Ac2O Pyr

187 X = OMP

188 X = SPh 73



+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3















Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331

































































Scheme (27)

Scheme (28)










O

BnO

OTBDPS

BnO X

SO Ph

O

BnO

OBn

BnO Li

SO Ph

DMF

OHO

HOOH

OH

O OH

OH

HO

OHOH

O

BnO

OTBDPS

BnO

SO Ph

O

OBn

OBnOBnSO

Ph

OH

131 X = Li

132 X = CHO

THF -100 oC

1 Ra-Ni

2 BH3 DMS NaOH H2O2

3 H2 PdC

131

133

134

OBnO

OBnOMe

BnO

Li

OBnO

BnOOBn

OBn

OOBn

OBnOMeBnO

OH

OBnO

BnOOBn

OBn

O

n-BuLi

BnO

OMe

BnO

BrBr

O

OBn

OHO

OH

OH

HO

OHO

OH

HO

OMe

O

BnO

OMeOBn

O

BnO

139 92

1BF3 OEt2 EtOH

2 H2 PdC AcOH

140 52 over 2 steps

135 136 137

138

CBr4 PPh3








Scheme (29)

O

BnO

BnOOBn

OBn

OOBn

OBnOMe

OBnOH

O

BnO

BnO

OBn

OBn

O

O

BnOOBn

OMe

BnO

Li

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnOBnO

OBn

OBnBnO

O

BnO

BnO

OBn

O

OBnO

OBn

OBnBnO

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OMe



1 BF3 OEt2 Et3 OH

2 H2 PtO2 EtOAc

145 76

1 H2 SO4 AcOH

2 PCC

146 62

repeat steps

repeat st eps

141 142

143

147

148


Scheme (30)

Scheme (31)

O

BnOOBn

OMe

Li

BnO

OPivBnO

OBn

OBn

BnO

O OO

BF3 OEt2

OBnO

OBn

OBn

BnO

OO

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

CAN

OBnO

OBn

OBn

BnO

OO

OO

BnOOBn

BnO

OMe

OHBnO

OBn

OBn

BnO

OHO

O

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

OPivBnO

OBn

OBn

BnO

OH OO

O

OMe

BnOOBn

BnO

OAcO

OAc

OAc

AcO

OAcOAc

OAcO

OAc

AcO

OMe

1

2 NaOMe MeOH


with a-isomer

1 Et3N Pyr H2O

2 H2 PdC H+

3 Ac2 O Pyr

149 151

152153

154 155

150

OBn

BnO

OBnO

OBn

BnO

OBnO

BnO

MeO

OBnO

OBn

BnO

O

OMe

AcO

OAcO

OAc

OAc

AcO

OAcO

OAc

O

BnOOBn

OMe

BnO

159 74 over 2 steps

+

BuLi ZnCl2 THF

1 H2 PdC2 Ac2O Pyr

156 157

158 59


Scheme (32)

Scheme (33)



OBnO

OBn

BnO

O

OBnO

ClZnO

OBn

BnOCl

R

OBnO

O

OBn

BnOCl

ZnR

O

ZnR

OBnO

OBn

BnO

160 161

162163

O

OBn

OBnBnO

O

O

OBn

OBnBnO H

TMS

O

OBn

OBnBnO H

O

OBn

BnO

OBnHO

O

OBn

OBnBnO OH

TMS

OBnBnO HO

OBn

TMS

O

OR

ORRO H

O

OR

RO

OR

OBn

OBnBnO

H

TMS

O+

K2CO3 MeOH

1 n-BuLi THF -78 oC

2 164

164165 66

166α 60 166β 13167 97


168 85

169 R = Bn 83


H2 (1 atm)Pd(OH) 2C

TMS-acetyl ene


-78 o C


O

OHCOBn

OBnBnO

OMe

O

CO2MeAcO

OAcAcHN

OAc

SO2

NAcO

OBnH

H

OBn

OBn

H

O

OMeH HH

A

O

CO2MeAcO

OAcAcHN

OAc

O

OBnOMe

OBnOBn

HO

AcO

+

Nu

174175

176

SmI2 THF

Scheme (34)

Scheme (35)

Scheme (36)

O

BnO

BnO

BnO

Si lylO

O2S N

O

BnO

HO R2R1

BnOBnO

SilylO

OBnO

BnO

BnO

SilylO

Sm(III)

R1COR2 SmI2 THF

171 172

173

NHBoc

OAcO

AcO

AcHN O

O

CO2BnO

OO

OO

OH

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

R2

O

CO2Me

AcHN

OAc

AcO

R1

AcO

AcO

AcHNO CO2Bn

NHBoc

AcO

OAc

O

Zn(BH4)2

180 R1 R2 = H OH ( RS 11)

181 R1 R2 = O

182 R1 = H R2 = OH de gt 90

DMSO Ac2O

177178

179

13 steps

22 equiv SmI2 THF


Scheme (37)

Fig (2)




4 CATIONIC METHODS


OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO


+

Ac2O Pyr

187 X = OMP

188 X = SPh 73



+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3















Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331







































































Scheme (29)

O

BnO

BnOOBn

OBn

OOBn

OBnOMe

OBnOH

O

BnO

BnO

OBn

OBn

O

O

BnOOBn

OMe

BnO

Li

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnOBnO

OBn

OBnBnO

O

BnO

BnO

OBn

O

OBnO

OBn

OBnBnO

OBnO

OBn

OBnBnO

OBnO

OBn

OBn

OMe

OBnO

OBn

OBnBnO

OMe



1 BF3 OEt2 Et3 OH

2 H2 PtO2 EtOAc

145 76

1 H2 SO4 AcOH

2 PCC

146 62

repeat steps

repeat st eps

141 142

143

147

148


Scheme (30)

Scheme (31)

O

BnOOBn

OMe

Li

BnO

OPivBnO

OBn

OBn

BnO

O OO

BF3 OEt2

OBnO

OBn

OBn

BnO

OO

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

CAN

OBnO

OBn

OBn

BnO

OO

OO

BnOOBn

BnO

OMe

OHBnO

OBn

OBn

BnO

OHO

O

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

OPivBnO

OBn

OBn

BnO

OH OO

O

OMe

BnOOBn

BnO

OAcO

OAc

OAc

AcO

OAcOAc

OAcO

OAc

AcO

OMe

1

2 NaOMe MeOH


with a-isomer

1 Et3N Pyr H2O

2 H2 PdC H+

3 Ac2 O Pyr

149 151

152153

154 155

150

OBn

BnO

OBnO

OBn

BnO

OBnO

BnO

MeO

OBnO

OBn

BnO

O

OMe

AcO

OAcO

OAc

OAc

AcO

OAcO

OAc

O

BnOOBn

OMe

BnO

159 74 over 2 steps

+

BuLi ZnCl2 THF

1 H2 PdC2 Ac2O Pyr

156 157

158 59


Scheme (32)

Scheme (33)



OBnO

OBn

BnO

O

OBnO

ClZnO

OBn

BnOCl

R

OBnO

O

OBn

BnOCl

ZnR

O

ZnR

OBnO

OBn

BnO

160 161

162163

O

OBn

OBnBnO

O

O

OBn

OBnBnO H

TMS

O

OBn

OBnBnO H

O

OBn

BnO

OBnHO

O

OBn

OBnBnO OH

TMS

OBnBnO HO

OBn

TMS

O

OR

ORRO H

O

OR

RO

OR

OBn

OBnBnO

H

TMS

O+

K2CO3 MeOH

1 n-BuLi THF -78 oC

2 164

164165 66

166α 60 166β 13167 97


168 85

169 R = Bn 83


H2 (1 atm)Pd(OH) 2C

TMS-acetyl ene


-78 o C


O

OHCOBn

OBnBnO

OMe

O

CO2MeAcO

OAcAcHN

OAc

SO2

NAcO

OBnH

H

OBn

OBn

H

O

OMeH HH

A

O

CO2MeAcO

OAcAcHN

OAc

O

OBnOMe

OBnOBn

HO

AcO

+

Nu

174175

176

SmI2 THF

Scheme (34)

Scheme (35)

Scheme (36)

O

BnO

BnO

BnO

Si lylO

O2S N

O

BnO

HO R2R1

BnOBnO

SilylO

OBnO

BnO

BnO

SilylO

Sm(III)

R1COR2 SmI2 THF

171 172

173

NHBoc

OAcO

AcO

AcHN O

O

CO2BnO

OO

OO

OH

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

R2

O

CO2Me

AcHN

OAc

AcO

R1

AcO

AcO

AcHNO CO2Bn

NHBoc

AcO

OAc

O

Zn(BH4)2

180 R1 R2 = H OH ( RS 11)

181 R1 R2 = O

182 R1 = H R2 = OH de gt 90

DMSO Ac2O

177178

179

13 steps

22 equiv SmI2 THF


Scheme (37)

Fig (2)




4 CATIONIC METHODS


OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO


+

Ac2O Pyr

187 X = OMP

188 X = SPh 73



+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3















Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331

































































Scheme (30)

Scheme (31)

O

BnOOBn

OMe

Li

BnO

OPivBnO

OBn

OBn

BnO

O OO

BF3 OEt2

OBnO

OBn

OBn

BnO

OO

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

CAN

OBnO

OBn

OBn

BnO

OO

OO

BnOOBn

BnO

OMe

OHBnO

OBn

OBn

BnO

OHO

O

O

OMe

BnOOBn

BnO

Co(CO)3

Co(CO)3

O

OPivBnO

OBn

OBn

BnO

OH OO

O

OMe

BnOOBn

BnO

OAcO

OAc

OAc

AcO

OAcOAc

OAcO

OAc

AcO

OMe

1

2 NaOMe MeOH


with a-isomer

1 Et3N Pyr H2O

2 H2 PdC H+

3 Ac2 O Pyr

149 151

152153

154 155

150

OBn

BnO

OBnO

OBn

BnO

OBnO

BnO

MeO

OBnO

OBn

BnO

O

OMe

AcO

OAcO

OAc

OAc

AcO

OAcO

OAc

O

BnOOBn

OMe

BnO

159 74 over 2 steps

+

BuLi ZnCl2 THF

1 H2 PdC2 Ac2O Pyr

156 157

158 59


Scheme (32)

Scheme (33)



OBnO

OBn

BnO

O

OBnO

ClZnO

OBn

BnOCl

R

OBnO

O

OBn

BnOCl

ZnR

O

ZnR

OBnO

OBn

BnO

160 161

162163

O

OBn

OBnBnO

O

O

OBn

OBnBnO H

TMS

O

OBn

OBnBnO H

O

OBn

BnO

OBnHO

O

OBn

OBnBnO OH

TMS

OBnBnO HO

OBn

TMS

O

OR

ORRO H

O

OR

RO

OR

OBn

OBnBnO

H

TMS

O+

K2CO3 MeOH

1 n-BuLi THF -78 oC

2 164

164165 66

166α 60 166β 13167 97


168 85

169 R = Bn 83


H2 (1 atm)Pd(OH) 2C

TMS-acetyl ene


-78 o C


O

OHCOBn

OBnBnO

OMe

O

CO2MeAcO

OAcAcHN

OAc

SO2

NAcO

OBnH

H

OBn

OBn

H

O

OMeH HH

A

O

CO2MeAcO

OAcAcHN

OAc

O

OBnOMe

OBnOBn

HO

AcO

+

Nu

174175

176

SmI2 THF

Scheme (34)

Scheme (35)

Scheme (36)

O

BnO

BnO

BnO

Si lylO

O2S N

O

BnO

HO R2R1

BnOBnO

SilylO

OBnO

BnO

BnO

SilylO

Sm(III)

R1COR2 SmI2 THF

171 172

173

NHBoc

OAcO

AcO

AcHN O

O

CO2BnO

OO

OO

OH

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

R2

O

CO2Me

AcHN

OAc

AcO

R1

AcO

AcO

AcHNO CO2Bn

NHBoc

AcO

OAc

O

Zn(BH4)2

180 R1 R2 = H OH ( RS 11)

181 R1 R2 = O

182 R1 = H R2 = OH de gt 90

DMSO Ac2O

177178

179

13 steps

22 equiv SmI2 THF


Scheme (37)

Fig (2)




4 CATIONIC METHODS


OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO


+

Ac2O Pyr

187 X = OMP

188 X = SPh 73



+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3















Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331

































































Scheme (32)

Scheme (33)



OBnO

OBn

BnO

O

OBnO

ClZnO

OBn

BnOCl

R

OBnO

O

OBn

BnOCl

ZnR

O

ZnR

OBnO

OBn

BnO

160 161

162163

O

OBn

OBnBnO

O

O

OBn

OBnBnO H

TMS

O

OBn

OBnBnO H

O

OBn

BnO

OBnHO

O

OBn

OBnBnO OH

TMS

OBnBnO HO

OBn

TMS

O

OR

ORRO H

O

OR

RO

OR

OBn

OBnBnO

H

TMS

O+

K2CO3 MeOH

1 n-BuLi THF -78 oC

2 164

164165 66

166α 60 166β 13167 97


168 85

169 R = Bn 83


H2 (1 atm)Pd(OH) 2C

TMS-acetyl ene


-78 o C


O

OHCOBn

OBnBnO

OMe

O

CO2MeAcO

OAcAcHN

OAc

SO2

NAcO

OBnH

H

OBn

OBn

H

O

OMeH HH

A

O

CO2MeAcO

OAcAcHN

OAc

O

OBnOMe

OBnOBn

HO

AcO

+

Nu

174175

176

SmI2 THF

Scheme (34)

Scheme (35)

Scheme (36)

O

BnO

BnO

BnO

Si lylO

O2S N

O

BnO

HO R2R1

BnOBnO

SilylO

OBnO

BnO

BnO

SilylO

Sm(III)

R1COR2 SmI2 THF

171 172

173

NHBoc

OAcO

AcO

AcHN O

O

CO2BnO

OO

OO

OH

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

R2

O

CO2Me

AcHN

OAc

AcO

R1

AcO

AcO

AcHNO CO2Bn

NHBoc

AcO

OAc

O

Zn(BH4)2

180 R1 R2 = H OH ( RS 11)

181 R1 R2 = O

182 R1 = H R2 = OH de gt 90

DMSO Ac2O

177178

179

13 steps

22 equiv SmI2 THF


Scheme (37)

Fig (2)




4 CATIONIC METHODS


OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO


+

Ac2O Pyr

187 X = OMP

188 X = SPh 73



+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3















Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331

































































O

OHCOBn

OBnBnO

OMe

O

CO2MeAcO

OAcAcHN

OAc

SO2

NAcO

OBnH

H

OBn

OBn

H

O

OMeH HH

A

O

CO2MeAcO

OAcAcHN

OAc

O

OBnOMe

OBnOBn

HO

AcO

+

Nu

174175

176

SmI2 THF

Scheme (34)

Scheme (35)

Scheme (36)

O

BnO

BnO

BnO

Si lylO

O2S N

O

BnO

HO R2R1

BnOBnO

SilylO

OBnO

BnO

BnO

SilylO

Sm(III)

R1COR2 SmI2 THF

171 172

173

NHBoc

OAcO

AcO

AcHN O

O

CO2BnO

OO

OO

OH

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

R2

O

CO2Me

AcHN

OAc

AcO

R1

AcO

AcO

AcHNO CO2Bn

NHBoc

AcO

OAc

O

Zn(BH4)2

180 R1 R2 = H OH ( RS 11)

181 R1 R2 = O

182 R1 = H R2 = OH de gt 90

DMSO Ac2O

177178

179

13 steps

22 equiv SmI2 THF


Scheme (37)

Fig (2)




4 CATIONIC METHODS


OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO


+

Ac2O Pyr

187 X = OMP

188 X = SPh 73



+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3















Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331

































































Scheme (37)

Fig (2)




4 CATIONIC METHODS


OAcAcHN

OAc

AcO

O

OBnBnO

OBnOMP

HO

O

MeO2CAcO

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

OBnOHC

OBnBnO

OMP

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OHHO

OHOMP

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

SO2Ph

O

MeO2CAcO

OAcAcHN

OAc

AcO

O

OAcAcO

OAcX

AcO


+

Ac2O Pyr

187 X = OMP

188 X = SPh 73



+

SmI2 THF183

179

185

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

OAcO

(CH2 )12 CH3

HN

OH

(CH2)14CH3

O

O

O

OHHO

OH

O

O

HO2 CHO

OAcAcHN

OH

HO

O

OHHO

OH

O(CH2)12CH3

HN

OH

(CH2)1 4CH3

GM4

GM3















Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331














































































Scheme (38)

O

CO2MeAcO

OAcAcHN

OAc

AcO

S(2-Py)

O

TESO

AcHNOMe

O

HO

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOAc

OAc

OAc

O

CO2MeAcO

OAcAcHN

OAc

AcO

O NHAcOBn

OTES

OMe

OAc

AcO

O NHAcOBn

OTES

OMeOH

O

CO2 MeAcO

OAcAcHN

+

192 65



25 equiv SmI2 THF


191 93

189

190


Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331

































































Scheme (39)

Scheme (40)

Scheme (41)

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBn

OBn

OBnO

OBnCH3

BnO

OH

CH2

OBnO

OBn

CH3

OBn

H2 O

BF3 OEt2 MeCN

194

195 96

OOAc

OAc

AcO

R SiMe3

SnCl4

O

OAc

AcO

R

O

OAc

AcO

O

OAc

AcO

Me3Si

R

SiMe3

196

197

Me3 Si SiMe3

O

AcO

OAc

OAc

SiMe3

SiMe3

O

AcO

OAc

O

OAc

OAc

O

AcO

AcOO

OAc

OAc

SnCl4 CH2Cl2

SnCl4 CH2Cl2198

199

200


Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331

































































Scheme (42)

Scheme (43)

AcO

OAc

OAc

Me3 Si

BnO

OBn

BnO

OBn

AcO

OAc

BnO

OBn

BnO

OBn

+ I2 CH2Cl2

202 88

198 201

O

OBn

OBn

O

O

O

OBn

OBn

O

O

OBn

OBn O

OBn

OBn

O

OPBH2M

OH

OBnO

BnO

BnO

O

OBn

OBn

O

OHOPMB

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

O

OBnOBn

O

Ph3P

O

O

OBn

OBn O

OBn

OBn

O

OPBM

OH

O O

CHO

OBn

BnO

OO

OBn

OBn

O

OHOPMB

BnO

BnO

BnO

OHO

HO

HO

O

OH

OHOH

OH

HOOMe

+ THF -78 oC

1 OsO4 pyr THF

2 NaH PMBBr

206a 206b 206a206b 61



1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 oC

1 PrSiH BF3 OEt2

2 H2 Pd(OH)2C

3 HCl MeOH 90 o C

203

204

205

207

209

208

210







Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331






































































Scheme (44)

OBnO

BnOOBn

OBn

P O

OEtOEtO

EtO

R H

OH

OH

OH

OH

O

R H

OH

OH

OH

OH

O

OHO

HOOH

OH

O

HO

OHOH

OH

OHO

HOOH

OH

O

HO

OH

OH

OHO

HOOH

OH

O

HO

OH

OHOH

R H

OH

OH

OH

OH

O

R

OBnO

BnOOBn

OBn

O

OHO

HOOH

OH

OO

HOHO

OH

R H

OH

OH

OH

OH

O

1 OsO4 NMO 50

2 DIBAL -32 oC 40

++ +

213 214 215 216

217 218 219 220


3 t-BuOK

4 I2 C6H6212

211







Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331






































































Scheme (45)

O

OBn

BnO

BnO

BnO

I

CrCl2-NiCl2O

OBn

OH

BnO

BnO

BnO

O

O

O

O

O

H

OBn

O

O

OBnBnO

BnO

BnO

OOBn

OBn

OAc

PMBOHOO

OBn

BnO

BnO

BnO

O

OBn

OBn

OAc

O

OH

HO

HO

HO

OH

OH

OH

O

OH

O

OBn

BnO

BnO

BnO

OBn

OBn

OAc

O

MMTr

+




221

222

223


1 AcOH2 TsCl pyr

3 NaH-imid4 DDQ

224225

226 227


Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331

































































Scheme (46)

OBnO O

OBn

OMe

OBn

XY

SMe

OBnBnO

O

OBn

OBn

OBn

OBn

O

BnO

YX

OBn

TBSO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

H

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

OHC OBn

OBn

OTBS

OMe

BnOOBn

CHO

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnOOBn

OBnO O

OBn

OMe

OBn

OBn

O

BnO

OMe

BnO

OBn

YX

OBnO O

OBn

OMe

OBn

OBn

O

BnO

O

OBn

OBn

OBn

OBn

O 1 LiHMDS

2

228

1 TBAF THF

2 MeSH BF3 OEt2

230 X = OH Y = H231 X = H Y = OH

230231 41



1 MsCl

2 liquid NH3


237a and 237b

NaBH4 MeOH

238

239 X = OBn


229

232233

234


Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331

































































Scheme (47)

OH C

O

O BnAcHN

OO

O

OBn OBnOBn

Br

O

OBn OBnOBn

O

OBnA cHN

OO

O TBSO

OBn O BnO Bn

O

OBnAcHN

OO

OTBS

S2

S1

S2

OTBSS1

O H

S2

OT BSS1

O H

MgBrMgBr

S2

O TBSS1

O H

S2

OHS1

OH

S2

OTBSS1

OH

O

OHHO

O H

O

HO

H OO

OBnA cH N

HO

H O

O

O HHO

OH

O

HOHO

O

OBnA cH N

HO

H O

O

OHH O

OH

O

H O

HOO

OBnAcHN

HO

HO

O

O HH O

OH

O

H O

H O O

OBnA cHN

HO

HO

O

O HH O

O H

O

HO

H O O

OBnAcHN

HO

HO

O

OHHO

OH

O

H O

O

OBnA cHN

HO

HOHO

+

241 242


243 244



245 246

1

2 T BAF 74

1

2 TBAF 88

247 248 249

250

251

250 251 1 1 252 253 1 1 254 255 1 1

252

253

254

255





Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331

































































Scheme (48)

O

OO

Se Ph

R

O

HO OHOH

O

OB n O B n

OB n

O B nO O

O O

R O OR

X

O

OO

R

Se Ph

O

HOOH

OH

O

OB nOB n

O Bn

OB n

O O

O O

R O O R

O H

O

O B n OB n

O B n

OB n

O

C HO

O

O O

R O OR

OAc HN

OAc

C O2NH 4HOOH

OH

O

OH O H

OH OH

O

OB n O B n

OB n

OB nO O

O O

R O OR

X

O

O

OAcOAc

C HOA cOOAc

OAc

O

OB n O B n

OB n

OB n

O

O Bn OB n

OB n

OB n

X

OH

OO

HOOH

OH

O

O

OMeOB n

OB nOB n

R

t-B uL i256 R = Li

257 R = L i

258

(R = t-B uMe 2Si )

(R = t-B uMe 2Si )



260 X = O R = t-B uMe 2Si ) 95

261 X = O R = t -B uMe2S i) 62

T e bbe re age nt

TB A F THF262 X = O R = H 94

diphosge ne

C H2C l 2Pyr

263 95

T HFH2O T FAr t


PhSe C l AgOT f

EtC N -80 oC

265

266


+

R =

1 Ac 2OPyr


4 NaO HT HFMe OH

5 Ac2O P yr


ste ps

268















OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331














































































OEt2



Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331

































































Scheme (49)

Bu3SnO

HOAcO

OMeOAc

OAc

O

AcO

OMeOAc

OAcI

AIBN

O

AcO

OMeOBn

OBn

HO2C O

AcO

OMeOR

ORY

X

OHBnO

BnO

OBn

OBnO

BnO

OBn

O

AcO

OMeOBn

OBnX

i-Pr i-Pr

N


O

RO

OMeOR

O

RO

OR

OR

RO

OR

278

I2 Ph3P

imidazole

269 270 93



OsO4 NaIO4

NaClO2 NaH2PO4

274 96

275

DCC 4-DMAP

276 X = O 82

277 X = CH2 51


1

2 BH3 THF H2O2 NaOH

H2 PdC EtOH

Ac2 O Pyr 4-DMAP

279 R = Bn R = H 64

280 R = R = H 99

281 R = R =Ac 97


Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331

































































Scheme (50)

Scheme (51)

O OOH

OH

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

H

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

O

O

OMe

OHH

OH

OMe

HHO

HO

OH

OH

286


2 (MeO)3CH BF3 90



TMEDA OsO4

Cat OsO4 NMO 287

Cat OsO4 NMO288

TMEDA OsO4

Cat OsO4 NMO

290

289

(RR)-282283

284

285

OHO

AcO

BrOAc

OAc

BnO

O

OBn

OBnO

OHO

AcOOAc

OAc

BnO

OOBn

OBnAcO

OHO

AcOOAc

OAc

BnO

O

OBn

OBnO

+

Bu3SnH AIBN291

292

293 81


294 56 over 2 steps


Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331

































































Scheme (52)

Scheme (53)

OBnO

BnOOBn

OBn O

OH

O

OBnO

BnO

OHOBn

OBn O

O

O

O

O

O

OBnO

BnOOBn

OBnO

OAcOAc

OAc

OBnO

BnO

OHOBn

OBn

IBu3SnH AIBN

295 297 26

1 BF3 OEt2 Et3SiH

2 L-Selectride THF


2 EtSiOSO2CF3 Ac2O


296

O

O

PhSeClO

O

PhSeCl

Bu3 SnH

O

O

PhSeCl

R

H

O

OAc

R

Cl

O

AcO

OAc

OAc

OAcOH

Cl

NHAc

R

OAc

AcHN

OH

O

OH OAc

OH

OHO

HO

OH

O

AcO

OAc

OAc

OAcBr

O

O

PhSeCl

O

O

PhSeCl

R

O

OTIPSAcHNR

OAc OAc

O

OHAcHN

COOMe

R

OAc

1 Bu4NF

2 NH3MeOH


1 Bu3 SnH AIBN2


1 H+ MeCN

2 H2 O NaHCO3

R =

1 O3MeOH

2 Me2S NaHCO3


furanoses +

304 56

305 68 306 84307 50

308 46

300 301 302

303

309






Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331





































































Scheme (54)

O

OH

Fuc

Cl

O

O

ClPhSe

OOAc

NHAcOHFuc

O

AcOOAc

AcO

Br

O

O

PhSeCl

O

AcOOAc

AcO

O

OH

PhSe Cl

Fuc

OOAc

NHAc

OMe

Fuc

O

AcHN

OH OAc

OH

O

OH

Me

OH

O

O

Fuc

ClSePh

O

HO

Fuc

ClSePh

+

Ph3SnHAIBN

78 combined yield

Fuc

310

+


313 40 314 355

1 mCPBA

2 Ac2O pyr DMAP

+

315 75

1 TfOH MeCN

2 NaHCO3 O3 -78 oC

316 10 over 2 steps

1 Cl3 CCN NaH

2 MeOH BF3 OEt2

317 79

1 LiBH4 THF

2 Dowex-H+

311

312a312b

318 70 for 2 steps






Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331





































































Scheme (55)

Scheme (56)

OO

OHSePh

OTBDPSO O

OO

SePh

OTBDPSO

OO

OBnOMe

OBn

Si

O

HOOBn

OMe

OBn

O

HOOH

OHHO

O

HOOH

OMe

OH

OTBDPSO

O

HOOBn

OMe

OBnO

OOH

1 n-BuLi THF

2 iPr2SiCl2 -78 oC

3 DMAP THF rt

1 Bu4NF THF

2 Dowex-H+

3 H2 PdC

Bu3SnH AIBN toluene

319

320

321

322323

OBnO

OHSePh

OBnBnO

OHO

OBnOMe

OBn

ROO

ROOH

OR

OHO

OROMe

OR

OBnO

O

OBnBnO

OO

OBnOMe

OBn

Si

SePh

OBnO

O

OBnBnOO

OOBn

OMe

OBn

Si

1 PhSeH Me2SiCl2

BuLi -78 oC

2 imidazole rt

Bu3SnH AIBN toluene

H2 PdC327 R = Bn

328 R = H

Bu4NF THF

324

320

325

326 45


CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331

































































CONCLUSIONS


ACKNOWLEDGEMENTS


REFERENCES










Scheme (57)

O

O

O

Ph

I

OMe

OHO

BnO

OH

OH

BnOOH

O

BnO

Si

O

O O

Ph

I

OMe

O

O

BnO

OR4O

R5O

OMe

OR2

OR3O

R3O

OR1

R3O

Bu3 SnH AIBN



334 R1 = R2 = R3 = R4 = R5 = H

335 R1 = R2 = R3 = R4 = R5 = Ac

329

H2 PdC MeOH

Ac2 O pyr

1 BuLi THF -78 oC

2 Me2SiCl2

3 DMAP

330

331





















































































































































Documents

Recent Advances in the Synthesis of C -oligosaccharides...Recent Advances in the Synthesis of C-oligosaccharides Current Topics in Medicinal Chemistry, 2005 , Vol. 5, No. 14 1395 Enone