Carbohydrate Research 344 (2009) 2336–2341

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Carbohydrate Research

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Addition of amines and carbon nucleophiles to vinyl sulfone-modified6-deoxy-hex-3-enopyranoside: a case of nucleophile dependentdiastereoselectivity

Rahul Bhattacharya, Tanmaya Pathak *

Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur 721 302, India

a r t i c l e i n f o a b s t r a c t

Article history:Received 30 July 2009Received in revised form 2 September 2009Accepted 9 September 2009Available online 12 September 2009

Keywords:Vinyl sulfoneModified carbohydrateMichael additionAminosugarBranched-chain sugarDiastereoselectivity

0008-6215/$ - see front matter � 2009 Elsevier Ltd. Adoi:10.1016/j.carres.2009.09.009

* Corresponding author.E-mail address: tpathak@chem.iitkgp.ernet.in (T. P

Reactions of amines and carbon nucleophiles with 4-sulfonyl-hex-3-enopyranoside generate a range ofC-3 amino- and C-3 branched-chain sugars, which are analogues of 3-amino-3,6-dideoxy sugars and3-C-branched-chain-3,6-dideoxy sugars. The diastereoselectivity of addition reaction is nucleophiledependent; while both nitrogen and carbon nucleophiles added in cis-fashion, amines generated C3-C4trans-diaxial products (gulo-derivatives), and carbon nucleophiles afforded C3–C4 trans-diequatorialproducts (gluco-analogues).

� 2009 Elsevier Ltd. All rights reserved.

1. Introduction

Aminosugars and branched-chain sugars are important classes ofmodified carbohydrates.1,2 Several 3-amino-3,6-dideoxy sugars and3-C-branched-chain-3,6-dideoxy sugars which belong to specialclasses of amino- and branched-chain sugars are reported in theliterature. Some of these aminosugars such as ristosamine,3,4 daun-osamine,3–6 ravidosamine,7,8 desosamine,9–12 and mycosamine13,14

are the structural components of either macrolide antibiotics suchas methamycine, pikromycine,13 and amphotericin B14 or tetracyc-lins such as ravidomycine7,8 and daunomycin15 (Fig. 1).

Although there are a limited number of reports on the naturaloccurrence of C-3-substituted-branched-chain sugars, D-aldgaroseis the best known example of this kind.16 However, a 3,6-dideoxybranched-chain sugar,17 namely, methyl 2-O-benzoyl-3,6-dide-oxy-3-C-methyl-a-D-altropyranoside was used for the constructionof the complex molecule rifamycin W. Yet another related sugarreportedly exists as a component of a complex molecule callipelto-side A, a novel class of antitumor agent (Fig. 2).18

In spite of the noted importance of C-3 functionalized 3,6-dide-oxysugars, synthesis of this class of compounds remains a chal-lenging task. Sugar triflates,12–14 epoxide,11 and ketones19,20 arethe commonly used intermediates for the incorporation of nitrogenfunctionality at C-3 of 6-deoxy-hexopyranosides. 4,6-Dichloro

ll rights reserved.

athak).

derivatives have also been used frequently for the synthesis of3-amino-3,6-dideoxysugars.11,20–22 3-Amino-3-deoxygluco-deriva-tives were generated in a regioselective fashion from 6-deoxy ana-logues of 2,3-anhydro allo-pyranosides.11 However because of thenonselective regiochemical outcome,21 the 3,4-anhydro allo- andgalacto-pyranosides are not the substrates of choice.23 On the otherhand, use of C-3-ulopyranosides for the synthesis of C-3-N amino-sugars are notably interesting compared to the other meth-ods,13,20,21 although the reduction of such sugar-derived oximeand hydrazone derivatives using common reducing agents affordeda mixture of aminosugars.8,19 In the case of C–C bond formation,nucleophilic displacement of C-3-O-sulfonylated carbohydratesby carbon nucleophiles are of negligible interest because of thesecondary nature of the C-3 hydroxyl groups. Although ring-open-ing reactions of sugar-derived epoxides by carbon nucleophiles areknown to be less efficient,23 limited number of 3-functionalized-3,6-dideoxysugars were synthesized by reacting the correspondingoxiranes with carbon nucleophiles.24–27 A minor method usingcyanopropionaldehyde diethylacetal and (S)-propyleneoxide gen-erated a mixture of four methyl glycosides of 3-cyano-2,3,4-6-tetradeoxysugars.28

2. Results and discussion

Vinyl sulfone-modified pyranosides and furanosides function asefficient Michael acceptors capable of generating a wide range ofproducts by reaction with several nucleophiles in a diastereoselec-

O

ArO2S

Me

OMeBnO BnO

MeO

OMe

ArO2S

Nu

NuH

Ar = p-Tol

?

?

1 2

Scheme 1. Proposed reaction pattern of vinyl sulfone-modified carbohydrate 1.

Me

MsOO

OMe

BzOBnO

MeO

OMe

STol-p

BzOBnO

MeO

OMe

OH

STol-p

BnO

MeO

OMe

OH

SO2Tol-p

BnO

43

6

1

MsCl, Py0 oC to + 4 oC16 h, 86%

p-TolSH, TMGDMF, 140 OC5 h, 89 %

NaOMe, MeOH reflux, 7 h, 97 %

MMPP,MeOH, rt, 6 h, quantitative

5

Scheme 2. Synthesis of methyl 2-O-benzyl-3,4,6-trideoxy-4-(4-methylphenyl)-sulfonyl-a-D-erythro-hex-3-enopyranoside 1.

OO

O

O

OH

OOH N

MeO

O

O

OH

OOH N

MeOO

O

O

O

OH OMe

OMeOH

AcOMe

Me2N

O

O

Me

OHOMe

O

O

OH

NMe2OH

OHMe

OH

OO

NH2OH

OOHOHMeO

OOH

OH OH

OH

OH

Me

Me OH

MeOH

COOH

Methymycine Pikromycine

Ravidomycine Daunomycine

Amphotericin B

Figure 1. 3-Amino-3,6-dideoxysugars as components of macrolide antibiotics andtetracyclins.

Me

OHO

OMe

OBz Me

OO

OMe

Me

OH OH

O

NH

O

O

OO

O

O

MeMe

MeO

HMe

OH

Me

OMe

O

Me

R

Cl

Cl

D-aldgarosemethyl 2-O-benzoyl-3,6-dideoxy-3-C-methyl-α-D-altropyranoside

Callipeltoside A

R =

Figure 2. Selected examples of C-3-branched-3,6-dideoxysugars.

R. Bhattacharya, T. Pathak / Carbohydrate Research 344 (2009) 2336–2341 2337

tive fashion.29,30 This strategy would also be useful for producing anumber of 3-deoxy-3-modified carbohydrates. Barring a report onthe use of 2-sulfonyl-hex-2-enopyranoside as a Michael acceptorand another describing the use of 4-sulfonyl-hex-3-enopyranosideas a partner in a cycloaddition reaction, this strategy for the func-tionalization of the C-3 carbon of a vinyl sulfone-modified carbo-hydrate remains unexplored.29,30 In the light of the abovediscussion and in order to study the scope of C-3 functionalizationwe intended to synthesize and study the reaction patterns of a 4-sulfonyl-hex-3-enopyranoside 1 derived from D-glucose. Weopined that a Michael acceptor like 1 is highly capable of generat-

ing both amino- and branched-chain sugars represented by thegeneral structure 2 (Scheme 1).

A retrosynthetic analysis of the route to 1 necessitated theintroduction of the tolylthio group at the C-4 position of a hexopyr-anosyl sugar. One of the easiest ways of forming a C–S bond wouldbe the displacement of suitably oriented and protected sugar-sul-fonates or the regioselective ring opening of epoxy-sugars withsulfur nucleophiles. The use of any 3,4-anhydro sugars as startingmaterials was ruled out because of the ambiguity of the ring-open-ing reaction in terms of regioselectivity discussed above.21,23 More-over, retrosynthetic analysis indicated that a higher number ofreaction steps would be required for the synthesis of suitablysubstituted 3,4-anhydro sugar (gluco- and galacto-) compared tothe synthesis of gluco-mesylate 3. Thus, the sugar-derived mesy-late 331 was reacted with p-tolylthiol in DMF in the presence ofTMG at about 150–160 �C to afford 4 in 89% yield within 5 h(Scheme 2). The regio- and stereospecificities of attack of p-tolyl-thiolate to C-4 position of 3 was a foregone conclusion becauseof its inbuilt structural features. Thus, the a-gluco-mesylate 3 pro-duced galacto-derivative 4 as expected. Treatment of compound 4with methanolic NaOMe at reflux temperature for 7 h affordedcompound 5 in excellent yield. The corresponding sulfone deriva-tive 6 was generated in quantitative yield at room temperaturewithin 6 h by oxidizing 5 with magnesium monoperoxyphthalatehexahydrate (MMPP) in MeOH. Compound 6 was subjected toelimination reaction using MsCl in pyridine at +4 �C to afford 1 in86% yield (Scheme 2). The identity of vinyl sulfone 1 was estab-lished on the basis of spectroscopic and analytical data, the vinylproton appearing at d 6.85.

2338 R. Bhattacharya, T. Pathak / Carbohydrate Research 344 (2009) 2336–2341

Compound 1 on reaction with neat benzylamine at 80–90 �Cgenerated a mixture (TLC) from which the major product 7 wasisolated in 79% yield (Scheme 3). Similarly, reaction of 1 with neatn-butylamine at elevated temperature afforded 8 in 83% yield. Aqammonia (30%) at room temperature produced a mixture fromwhich the major product 9 was isolated in 81% yield; the productwas however characterized as the N-benzoyl derivative 10. Com-pound 1 on the other hand, on reaction with carbon nucleophilesgenerated from nitromethane or dimethylmalonate in the presenceof t-BuOK in THF at reflux temperature, afforded single compounds11 and 12 in 73% and 78% yields, respectively (Scheme 3).

The structure of compound 7 was unambiguously established asthe gulo-derivative from X-ray crystal structure analysis of the sin-gle crystal of compound 7 (Fig. 3). On the basis of similarities of the

Figure 3. ORTEP diagram of compound 7.

MeO

OMeNHR

SO2Tol-p

BnO

Me

p-TolO2SO

OMeR

BnO

1 BzCl, Py, rt, 20 h, 88%

7 R = Bn (79%) 8 R = n-Bu (83%) 9 R = H (81%)10 R= Bz

neat aminesoraq. NH3

11 R = CH2NO2 (73%)12 R = CH(CO2Me)2 (78%)

CH3NO2orH2C(COOMe)2

KOBu-t, THF,80 ºC, 10-12 h

Scheme 3. Reactions of vinyl sulfone-modified 6-deoxy-hex-3-enopyranoside 1with amines and carbon nucleophiles.

spectral data of amino-derivatives 8 (d 4.71, J = 3.6 Hz, H-1), 10 (d4.94, J = 3.6 Hz, H-1), and 7 (d 4.74, J = 3.6 Hz, H-1) we concludedthat amine adducts 8–10 were having D-gulo conformation as well.The identities of compounds 11 (Fig. 4) and 12 (Fig. 5) were estab-lished unambiguously by the X-ray analysis of their single crystalsand the compounds were found to have D-gluco configuration.

Since amines were expected to add to the C-3 position of 1 froma direction opposite to that of the disposition of the C-2 benzyloxygroup to afford a D-gluco derivative having four (C2, C3, C4, and C5)equatorial bonds, the formation of products with C–N axial bond atC-3 and C–S axial bond at C-4 surprised us. However, it is reportedthat the addition of neutral species like amines to a Michael accep-tor may take place through concerted mechanism involving a pro-ton relay process.32 Considering the same mechanistic pathway,we propose that cis-addition of amines to compound 1 takes placeto generate the trans-diaxial product (Scheme 4). Thus, it is plausi-ble that the preferential formation of trans-diaxial geometry in thetransition state over the trans-diequatorial geometry resulted fromthe positioning of amines via a six-membered transition state asdepicted in Scheme 4. It is also probable that an additional H-bond-ing such as R–N���H���OMe stabilized the transition state further tosuch an extent that the formation of tetra-equatorial products(such as 11 and 12) was overruled in favor of the formation ofC3–C4 diaxial products 7–9.33–35

Figure 4. ORTEP diagram of compound 11.

Figure 5. ORTEP diagram of compound 12.

O

CH3

OMeO

H

NN

H

H

R

HR

H

7-9

Bn

p-TolO 2S

Scheme 4. Proposed concerted proton relay process leading to the formation ofD-gulo derivatives 7–9.

R. Bhattacharya, T. Pathak / Carbohydrate Research 344 (2009) 2336–2341 2339

Compound 3 on reaction with nitromethane and dimethylmal-onate generated the expected and thermodynamically more stableC3–C4 diequatorial products. Although it is tempting to argue thatthe bulky benzyloxy substituent at C-2 was responsible for the par-ticular diastereoselectivity of the addition of carbon nucleophilesat C-3, it is also highly probable that the anomeric a-methoxygroup which stabilized the transition state in case of amines(Scheme 4), stereoelectronically repelled the incoming negativelycharged carbon nucleophiles so that these nucleophiles wereforced to attack the electron deficient C-3 position of 1 from theb-face of the sugar ring.33–35

In conclusion, the study on the reaction pattern of the hithertounknown 6-deoxy-4-sulfonyl-hex-3-enopyranoside 1 highlightsonce again on the efficiency and diastereoselectivity of the additionof nitrogen and carbon nucleophiles to such systems. This vinylsulfone-modified carbohydrate is capable of generating rare ami-nosugars having a D-gulo configuration. In contrast, the same start-ing molecule generates less known C-3 branched-chain sugarswith D-gluco configuration.

3. Experimental

3.1. General methods

All reactions were conducted under N2 atmosphere. Meltingpoints were determined in open-end capillary tubes and are uncor-rected. Carbohydrates and other fine chemicals were obtained fromcommercial suppliers and are used without purification. Solventswere dried and distilled following the standard procedures. TLCwas carried out on pre-coated plates (Merck Silica Gel 60, f254) andthe spots were visualized with UV light or by charring the platedipped in 5% H2SO4–MeOH solution. Column chromatography wasperformed on silica gel (230–400 mesh). 1H and 13C NMR for mostof the compounds were recorded at 200/400 and 50/100 MHz,respectively, using either CDCl3 as the solvent unless stated other-wise. DEPT experiments have been carried out to identify the meth-ylene carbons. Optical rotations were recorded at 589 nm.

3.2. Methyl 2-O-benzyl-3-O-benzoyl-4,6-dideoxy-4-(4-methylphenyl)-sulfide-a-D-galactopyranoside 4

To a well-stirred solution of p-thiocresol (3.45 g, 27.77 mmol)and TMG (3.31 g, 26.36 mmol) in dry DMF (20 mL) was added asolution of the known compound 3 (2.5 g, 5.55 mmol) in dryDMF (10 mL). The resulting solution was heated at 140–150 �C un-der N2 for a period of 6 h, cooled to rt, and poured into satd aq NaClsolution (80 mL). The mixture was extracted with EtOAc(3 � 30 mL) and separated. The EtOAc layer was dried over anhydNa2SO4, and evaporated under reduced pressure. The resulting syr-up was purified over silica gel to yield 4 (2.36 g, 89%). [Eluent:EtOAc/pet ether (1:19)] Colorless jelly. ½a�30

D +52.2 (c 1.14, CHCl3).1H NMR (CDCl3): d 1.42 (d, 3H, J = 6.4 Hz); 2.07 (s, 3H); 3.36 (s,3H); 3.84–3.87 (m, 1H); 4.14–4.21 (m, 1H); 4.36–4.45 (m, 1H);4.66–4.82 (m, 3H); 5.54–5.61 (m, 1H); 6.74 (d, 2H, J = 8.0 Hz);

7.14 (d, 2H, J = 8.0 Hz); 7.21–7.39 (m, 8H); 7.49–7.56 (m, 1H);7.81–7.85 (m, 1H). 13C NMR: d 18.5, 21.6, 55.4, 57.6, 65.3, 73.3,73.4 (CH2), 74.6, 98.7, 127.8, 127.9, 128.0, 128.4, 129.5, 129.6,129.9, 132.0, 132.1, 132.7, 136.6, 138.1, 165.8. Anal. Calcd forC24H30O5S�0.5H2O: C, 63.95; H, 6.77. Found: C, 63.86; H, 7.03.

3.3. Methyl 2-O-benzyl-4,6-dideoxy-4-(4-methylphenyl)-sulfide-a-D-galactopyranoside 5

To a solution of 4 (2.0 g, 4.18 mmol) in methanol (30 mL) wasadded NaOMe (0.3 g, 5.55 mmol) and the resulting solution washeated under reflux for 7 h, cooled to rt and the solvent was evapo-rated. The residue thus obtained was dissolved in EtOAc (30 mL).The organic layer was washed with satd aq NH4Cl solution(2 � 20 mL) and separated. The organic layer was dried over anhydNa2SO4, and evaporated under reduced pressure to get crude 5.The crude product was purified over silica gel to get pure compound5 (1.63 g, 97%). [Eluent: EtOAc/pet ether (3:17)]. Colorless jelly. ½a�30

D

+48.4 (c 0.625, CHCl3). 1H NMR (CDCl3): d 1.36 (d, 3H, J = 6.4 Hz); 2.31(s, 3H); 2.79 (br s, 1H); 3.33 (s, 3H); 3.39–3.41 (m, 1H); 3.46–3.50 (m,1H); 4.20–4.29 (m, 2H); 4.60 (d, 1H, J = 3.6 Hz); 4.74 (dd, 2H,J = 12.0 Hz, 50.8 Hz); 7.09 (d, 2H, J = 8.0 Hz); 7.28–7.43 (m, 7H). 13CNMR: d 18.4, 21.0, 55.3, 62.8, 65.6, 69.3, 73.1 (CH2), 78.3, 98.3,127.9, 128.1, 128.4, 129.8, 132.0, 133.1, 137.1, 138.1. Anal. Calcdfor C21H26O4S�H2O: C, 67.91; H, 6.04. Found: C, 67.84; H, 5.51.

3.4. Methyl 2-O-benzyl-4,6-dideoxy-4-(4-methylphenyl)-sulfonyl-a-D-galactopyranoside 6

To a solution of compound 5 (1.64 g, 4.18 mmol) in MeOH(30 mL) was added MMPP (8.27 g, 16.72 mmol). The reaction mix-ture was stirred for 6 h at ambient temperature, filtered, and thefiltrate was evaporated under reduced pressure. The resulting res-idue was neutralized with satd aq NaHCO3 (70 mL). The mixturewas extracted with EtOAc (3 � 30 mL). The organic layer was sep-arated and dried over anhyd Na2SO4 and filtered. The filtrate wasconcentrated to dryness under reduced pressure and purified oversilica gel to yield compound 6 (1.6 g, quantitative). [Eluent: EtOAc/pet ether (1:4)]. Colorless jelly. ½a�30

D +47.3 (c 0.62, CHCl3). 1H NMR(CDCl3): d 1.68 (d, 3H, J = 7.2 Hz); 2.47 (s, 3H); 3.43 (s, 3H); 3.73–3.77 (m, 2H); 3.86 (d, 1H, J = 2.4 Hz); 4.13–4.14 (m, 1H); 4.53–4.58 (m, 2H); 4.71 (d, 1H, J = 12.0 Hz); 4.89 (s, 1H); 7.14–7.31 (m,5H); 7.35 (d, 2H, J = 8.0 Hz); 7.75 (d, 2H, J = 8.0 Hz). 13C NMR: d17.5, 21.6, 56.3, 63.8, 66.9, 68.4, 73.6 (CH2), 75.4, 95.8, 127.7,127.8, 128.1, 128.2, 129.9, 136.6, 137.9, 145.1. Anal. Calcd forC21H26O6S: C, 67.04; H, 6.82. Found: C, 67.20; H, 75.

3.5. Methyl 2-O-benzyl-3,4,6-trideoxy-4-(4-methylphenyl)-sulfonyl-a-D-erythro-hex-3-enopyranoside 1

To a solution of 6 (1.0 g, 2.46 mmol) in dry pyridine (15 mL) wasadded methanesulfonyl chloride (0.55 mL, 7.4 mmol) in dry pyri-dine (5 mL) at 0 �C. The mixture was left overnight at 4 �C. Thereaction mixture was poured into satd aq NaHCO3 (70 mL) andaq phase was extracted with dichloromethane (3 � 30 mL). Organ-ic extracts were pooled together, dried over anhyd Na2SO4, and fil-tered. Et3N (5 mL) was added to the filtrate and after 15 min thesolvent was evaporated under reduced pressure. The resulting res-idue was purified over silica gel to get 1 (0.79 g, 83%). [Eluent:EtOAc/pet ether (1:4)] White solid. Mp: 156–157 �C. ½a�30

D +27.1 (c0.30, CHCl3). 1H NMR (CDCl3): d 1.34 (d, 3H, J = 6.5 Hz); 2.43 (s,3H); 3.33 (s, 3H); 4.16–4.27 (m, 2H); 4.66–4.76 (m, 3H); 6.85 (d,1H, J = 1.26 Hz); 7.25–7.43 (m, 7H); 7.74 (d, 2H, J = 8.0 Hz). 13CNMR: d 19.7, 21.5, 55.6, 64.3, 71.4, 71.7 (CH2), 96.1, 127.8, 128.0,128.1, 128.5, 129.7, 135.4, 136.5, 137.0, 142.2, 144.4. Anal. Calcdfor C21H24O5S�0.5CHCl3: C, 57.62; H, 5.51. Found: C, 57.65; H, 5.39.

2340 R. Bhattacharya, T. Pathak / Carbohydrate Research 344 (2009) 2336–2341

3.6. Methyl 2-O-benzyl-3,4,6-trideoxy-3-benzylamino-4-(4-methylphenyl)-sulfonyl-a-D-gulopyranoside 7

A mixture of 1 (0.2 g, 0.5 mmol) and neat benzylamine (3 mL)was heated at 90 �C for 16 h with continuous stirring under N2.The reaction mixture was cooled to room temperature and the vol-atile matters were evaporated under reduced pressure. The residueobtained was dissolved in EtOAc (30 mL). The EtOAc layer waswashed with satd aq solution of NH4Cl (3 � 30 mL) and separated.The organic layer was then dried over anhydrous Na2SO4, filtered,and the filtrate was evaporated under reduced pressure to get aresidue. The crude residue was purified by column chromatogra-phy over silica gel to get 7 (0.136 g, 79%). [Eluent: EtOAc/pet ether(1:3)] White crystalline solid. Mp: 127–129 �C. ½a�28

D +34.1 (c 0.625,CHCl3). 1H NMR (CDCl3): d 1.51 (d, 3H, J = 6.8 Hz); 2.44 (s, 3H),3.15–3.16 (m, 1H), 3.28–3.30 (m, 1H), 3.41 (s, 3H); 3.57 (dd, 2H,J = 13.6, 36.0 Hz), 3.99–4.02 (m, 1H); 4.37 (dd, 2H, J = 12.4,32.8 Hz); 4.69–4.72 (m, 1H); 4.74 (d, 1H, J = 3.6 Hz); 7.01–7.02(m, 2H); 7.19–7.26 (m, 7H); 7.29–7.36 (m, 3H); 7.46 (d, 2H,J = 8.0 Hz). 13C NMR: d 18.4, 21.8, 52.7 (CH2), 52.8, 55.3, 60.7,68.8 (CH2), 75.0, 96.0 (CH), 101.2 (CH), 118.0 (C), 120.6 (CH andC), 122.8 (C), 126.6 (CH), 128.3 (CH), 129.1 (CH), 138.5 (C). 160.6(C). Anal. Calcd for C28H33NO5S�0.5CH3OH: C, 62.45; H, 6.77; N,3.03. Found: C, 62.63; H, 5.51; N, 2.96.

3.7. Methyl 2-O-benzyl-3,4,6-trideoxy-3-(n-butyl)amino-4-(4-methylphenyl)-sulfonyl-a-D-gulopyranoside 8

Compound 1 (0.2 g, 0.5 mmol) was treated with neat n-butyl-amine (3 mL) at 80 �C following the procedure described for 7 toget compound 8 within 14 h (0.142 g, 83%). [Eluent: EtOAc/petether (1:4)]. White crystalline solid. Mp: 123–125 �C. ½a�28

D +28.1(c 0.625, CHCl3). 1H NMR (CDCl3): d 0.80 (t, 3H, J = 6.8 Hz); 1.14–1.18 (m, 5H); 1.52 (d, 3H, J = 7.2 Hz); 2.31–2.34 (m, 2H); 2.43 (s,3H), 3.22–3.25 (m, 2H), 3.39 (s, 3H); 4.00–4.02 (m, 1H), 4.58–4.64 (m, 3H); 4.71 (d, 1H, J = 3.6 Hz); 7.26–7.38 (m, 7H); 7.66 (d,2H, J = 8.4 Hz). 13C NMR: d 13.9, 18.3, 20.3 (CH2), 21.7, 31.9 (CH2),49.0 (CH2), 54.2, 55.9, 61.0, 67.8, 71.3, 71.6 (CH2), 98.9, 128.0,128.1, 128.2, 128.5, 129.7, 137.7, 137.8, 144.5. Anal. Calcd forC25H36NO5S�0.5CH3OH: C, 65.62; H, 7.40; N, 2.89. Found: C,65.69; H, 7.57; N, 2.79.

3.8. Methyl 2-O-benzyl-3,4,6-trideoxy-3-(N-benzoyl)amino-4-(4-methylphenyl)-sulfonyl-a-D-gulopyranoside 10

Compound 1 (0.2 g, 0.5 mmol) was treated with aq ammonia atroom temperature to get compound 9 within 36 h. Compound 9was benzoylated using standard procedure to afford 10 (0.18 g,88% from 1). [Eluent: EtOAc/pet ether (1:6)]. Colorless jelly. ½a�28

D

+54.1 (0.625, THF). 1H NMR (CDCl3): d 1.58 (d, 3H, J = 6.8 Hz);2.46 (s, 3H), 3.51 (s, 3H); 3.75–3.77 (m, 1H), 4.29–4.31(m, 1H); 4.46–4.58 (m, 3H); 4.65–4.69 (m, 1H); 4.49 (d, 1H,J = 3.6 Hz); 7.26–7.34 (m, 5H); 7.38–7.52 (m, 5H); 7.70 (d, 2H,J = 7.2 Hz); 7.83 (d, 2H, J = 8.4 Hz). 13C NMR: d 18.4, 21.8, 46.7,56.2, 60.9, 64.9, 69.3, 70.9 (CH2), 99.3, 127.0, 128.0, 128.2(2 � CH), 128.6, 128.7, 130.0, 131.9, 133.6, 137.0, 137.1, 145.0,167.0. Anal. Calcd for C28H31NO6S�0.5H2O: C, 63.40; H, 5.60; N,2.76. Found: C, 63.22; H, 5.62; N, 2.29.

3.9. Methyl 2-O-benzyl-3,4,6-trideoxy-3-C-nitromethyl-4-(4-methylphenyl)-sulfonyl-a-D-glucopyranoside 11

To a suspension of 90% tBuOK (0.33 g, 2.94 mmol) in dry THF(5 mL) at 0 �C was added CH3NO2 (0.15 mL, �2.5 mmol) and theresulting solution was stirred for 15 min. at that temperature un-der N2. A solution of 1 (0.2 g, 0.5 mmol) in dry THF (10 mL) was

added dropwise to the reaction mixture. The resulting solutionwas then heated under reflux with continuous stirring under N2

for 12 h. The reaction mixture was cooled to room temperatureand the volatile matters were evaporated under reduced pressure.The residue obtained was triturated with EtOAc (30 mL). The or-ganic layer was washed with satd aq solution of NH4Cl(3 � 30 mL) and separated. The organic layer was dried over anhydNa2SO4, filtered, and the filtrate was evaporated under reducedpressure to get a residue. The crude residue was purified by col-umn chromatography over silica gel to obtain 11. (0.13 g, 73%).[Eluent: EtOAc/pet ether (1:4)]. White crystalline solid. Mp: 137–139 �C. ½a�28

D +34.3 (c 0.625, CHCl3). 1H NMR (CDCl3): d 1.30 (d,3H, J = 6.4 Hz); 2.46 (s, 3H); 2.87–2.94 (m, 1H); 3.18 (s, 3H);3.49–3.55 (m, 2H); 3.88–3.92 (m, 1H); 4.47 (d, 1H, J = 3.2 Hz);4.55 (dd, 2H, J = 11.6, 18.4 Hz); 5.06–5.10 (m, 1H); 5.19–5.24 (m,1H); 7.29–7.40 (m, 7H); 7.76 (d, 2H, J = 8.0 Hz). 13C NMR: d 21.1,21.6, 34.8, 55.2, 62.9, 66.0, 72.6 (CH2), 73.8 (CH2), 75.4, 95.2,128.2, 128.3, 128.6, 128.8, 130.1, 135.0, 137.1, 145.5. Anal. Calcdfor C22H27NO7S�0.5H2O: C, 64.90; H, 6.19; N, 2.07. Found: C,64.90; H, 5.99; N, 1.95.

3.10. Methyl 2-O-benzyl-3,4,-trideoxy-3-C-bis(methoxycarbonyl)methyl-4-(4-methylphenyl)-sulfonyl-D-glucopyranoside 14

Compound 1 (0.2 g, 0.5 mmol) was treated with dimethylmalo-nate (0.15 mL, �2.5 mmol) following the procedure described forthe preparation of 11 to get compound 12 within 10 h. (0.14 g,78%). [Eluent: EtOAc/pet ether (2:7)] White crystalline solid. Mp:142–144 �C. ½a�28

D +37.1 (c 0.625, CHCl3). 1H NMR (CDCl3): d 1.45(d, 3H, J = 5.6 Hz); 2.45 (s, 3H); 2.99–3.05 (m, 4H); 3.14–3.20 (m,1H); 3.47 (s, 3H); 3.79 (s, 3H); 3.80–3.84 (m, 1H); 4.22 (d, 1H,J = 2.8 Hz); 4.26–4.35 (m, 2H); 4.45 (d, 1H, J = 11.6 Hz); 4.77 (d,1H, J = 3.2 Hz); 7.22–7.29 (m, 5H); 7.37 (d, 2H, J = 8.0 Hz); 7.77(d, 2H, J = 8.0 Hz). 13C NMR: d 21.6, 21.9, 36.4, 49.6, 52.2, 52.3,54.9, 62.6, 68.2, 72.8 (CH2), 75.0, 95.6, 127.9, 128.2, 128.6, 129.3,129.8, 134.1, 137.7, 145.1. Anal. Calcd for C26H32O9S�0.5H2O: C,62.67; H, 5.59. Found: C, 62.40; H, 5.82.

Acknowledgments

T.P. thanks the Indo-French Centre for the Promotion of Ad-vanced Research, New Delhi for funding (Project No. 3405-1). R.B.thanks CSIR, New Delhi for a fellowship. DST is also thanked forthe creation of 400 MHz facility under IRPHA program and DST-FIST for single crystal X-ray facility.

Supplementary data

Complete crystallographic data for the structural analysis havebeen deposited with the Cambridge Crystallographic Data Centre,CCDC Nos. 742104–742106. Copies of this information may be ob-tained free of charge from the Director, Cambridge CrystallographicData Centre, 12 Union Road, Cambridge, CB21EZ, UK. (fax: +44-1223-336033, e-mail: deposit@ccdc.cam.ac.uk or via: www.ccdc.cam.ac.uk), and spectra of 1, 4–8, 10–12. Supplementary dataassociated with this article can be found, in the online version, atdoi:10.1016/j.carres.2009.09.009.

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