Tetrahedron. Vol. 53. No. I, pp. 109-l 18, 1997

CopyrIght 0 1996 Elsevier Science Ltd

Printed in Great Britatn All rights reserved

0040.4020/97 $17.00 + 0.00 PII: SOO40-4020(96)00956-S

Synthesis of Tolypocladin and Isotolypocladin

Waiter Werner*, Udo Griife and Wolfgang ihn

Hans-Knoll-lnstitut fir Naturstoff-Forschung e. V

Beutenbergstrage 11, D-07745 Jena, Postfach 100813, D-07708 Jena

Dieter Tresselt and Stefan Winter

Institut fiir Molekulare Biotechnologie e. V.

Beutenbergstrage 11, D-07745 Jena

Erich Paulus

Hoechst AC, D-65926 Frankfurt/Main

Postfach 800320

Abstract: Total synthesis of the microbial metabolik toly~ladin (1) and isomcric isotolypocladin (2)

is described using Fnedel-Crafts acylatlon for condensation of the l-aza-anthraquinone-(9. IO) ring.

Copyright 0 1996 Elsevier Science Ltd

1NTRODUCTION

Tolypocladin (1) was isolated recently from Ibfypocludium it$arum DSM 915 and identified as 3-

methyl-5,6 (or 7),8-trihydroxy-2-aza-anthraquinone-(9,lO)’. Apparently, its structure is related to bostrycoidin

(la) from Fusarium solutti D2 purpk as the appropriate 6-methoxy derivative.’

OR’ 0

R20

OR3 0

1: R’, R’, R’ = H Tolypocladin 2: R’, R’, Rj = H Isotolypocladin

la: R’, R’, = H, R’ = Me Bostrycoidin 2a: R’, R’ = H, R’ = Me Isobostrycoidin

1 b: R’, R’, Ri = AC Triacetyl-tolypocladin 2b: R’, R’, R3 = AC Triacetyl-isotolypocladin

Though the NMR data settled most details of the chemical constitution of 1, chemical total synthesis was

necessary to determine the exact position of one of the hydroxy groups, located either at C-6 or C-7 atom of the

aromatic skeleton.

109

II0 W. WERNER et ul.

CamerorP5 and Watanabe” synthesized la via a series of rather diecult steps in low yields because the

commonly used Friedel-Crafts synthesis failed to give reasonable results. Thus, Cameron et al. first prepared 2-

methyl-6,8-dimethoxy-2-aza-anthraquinone-(9,lO) by the addition of I,l-dimethoxy ethene to 3-methyl-

isoquinoline quinone (which is rather hardly accessible) as well as through radical acylation of 4-cyano-Z-

methyl-pyridine by 3,5-dimethoxy-benzaldehyde, followed by ring closure. The resulting key intermediate was

photooxidized and demethylated partially to yield la. Moreover, Watanabe et al. condensed a lithiated nicotinic

acid amide with a trimethoxy-benzoic acid amide. There after, the pyridine ring was methylated in position 2,

followed by reduction, ring closure, oxidation and partial demethylation.

Here we report on a new approach to 1, la and 2, 2a via Friedel-Crafts acylation which demonstrates

this route’ to be more encouraging than in the past

RESULTS AND DlSCUSSlON

The first step of our synthesis was the condensation of l,2,4-trimethoxy-benzene (3) and 2-methyi-

pyridine 4,5-dicarboxyiic acid anhydride (4 ) under Friedel-Crafts conditions (Scheme I). Although formation of

not less than six structural isomers (3 protons in 3, 2 acyl groups in 4) appeared as possible, the acylation

occurred regioselectively at position 5 of 3, but the educt 4 reacted with each acyi group in different manners

The resulting key products 5 and 6 (Scheme I) can be separated by recrystallization

0

0 I= (2, KN

ci 4

cH,- 5

+AICI, / CH,CI,

\ W &SO,, c

-2

&CO

Scheme 1

The ‘H NMR spectra of 5 and 6 show two singlets of the remaining protons in positions 3’ and 6’ at the

benzene ring. As neither ortho nor meta coupled protons have been observed, H-3’ and H-6’ are located in para

position (Scheme 2). Conclusive evidence of hydroxyl position in 1 and 2 was readily inferred from the chemical

shift data of the protons in 6 and 7 observed after Clemmensen reduction of the carbonyl group to the methyiene

compound 7 (Scheme 2).

Synthesis of tolypocladin and isotolypocladin III

Scheme 2

Table 1: ‘H NMK data, S [ppm] ofthe aromatic hydrogen atoms in 6 and 7, CDCl:

H Atoms 66 67 6647

H-3’ 6.67 s 6.68 s -0.01

H-6 7.10 s 6.76 s to.34

H-3 7.38 s 6.86 s +0.52

H-6 li 92 s 8 77 s +o I5

The greatest changes of the chemical shifts 6 have been observed for H-6’ and H-3 neighboured to the

carbonyl and methylene groups (Table 1). Due to this position 7 is unequivocally proved for the hydroxyl group

in 2 and vice versa position 6 for HO substituent in 1. Consequently, cyclization and demethylation of the key

products 5 and 6 by sulfuric acid yielded 1 and 2 (Scheme I ). Traces of bostrycoidin (la) and/or isobostrycoidin

(2a) were detected by EI/MS (Mf: m/z 285) as further products of the cyclocondensation due to the incomplete

demethylation.

The purification of 1 and 2 by recrystallization or preparative chromatography is nearly impossible,

because of intermolecular hydrogen bonds and insufftcient solubility, but the easily accessible triacetyl derivatives

ib and 2b do not possess these disadvantages and they are suitable for recrystallization or column

chromatography. You can get back pure 1 and 2 by saponitication of lb and 2b. Thin layer chromatography

(TLC) and column chromatography are possible, if the silica gel sheets or adsorbents are prepared with a

methanolic oxalic acid solution

The isomers 1 and 2 are discernible by characteristic physico-chemical differences. The El/MS

fragmention pattern of 2 displays less fragments than that of 1. Even the melting behaviour of 2 is characteristic

in comparison to I: The microcrystalline shape of 2 changes at 230 “C to long red needles, which melt under

decomposition while the microcrystalline 1 does not change its shape. The TLC spot of 2 fluoresces orange at h

366 nm, but 1 fluoresces pale violet.- The ‘H NMR spectrum of 1 displays three distinguishable HO signals,

whiie that of 2 indicates only one signal at 13. I8 ppm attributable to two HO protons. However, high dilution of

2 in DMSO-d6 yielded significant shit? changes of signals towards deeper (or higher) field, probably due to the

degradation of intermolecular associates, which are present in higher concentrated solutions.

112 W. WERNER et al

Figure I. Molecular structure of 2 with the thermal elhpsods (20%) and the atomic numbering.

The differences in the NMR spectra of 1 and 2 were the reason to measure the X-ray diffraction of 2

crystals (from chloroform/ethyl acetate), in order to examine if there are any differences in their structures too. it

is shown in Figure I the molecular structure of 2. The molecule is about planar. The dihedral angles of the two

terminal benzene rings to the central para quinone ring are 2(2)” and 3(2)0 respectively. Figures 2-4 display the

projections of the crystal structure of 2 along the O-x, O-y, and the O-z-axis. In Figures 2 and 3 it is shown, that

two molecules are linked by two intermolecular N2...H07 hydrogen bonds (2.735 -6). No other intermolecular

hydrogen bonds are possible. There are, however, two intramolecular hydrogen bonds (008...009, 005...0010;

2.600 and 2.585 4 respectively). Figure 4 displays the crystal structure with molecuIe chains, parallel to the

crystallographic z-axis. The intramolecular distances show too, that the central ring, at least in the crystal, is

para-quinoid.’

Figure 2. Projection of the crystal structure of 2 along the x-axis.

Synthesis of tolypocladin and isotolypocladin 113

Figure 3. Projcclion of the crystal strudurc of2 along the y-axis. Figure 4. Projection of the IX~UI slruciurc

of 2 along the z-am.

The biological role of metabolites as 1, either as metal-chelating agents or of constituents of a particular

respiratory chain, has been subject to discussion. ’ The biological importance of pigment production for the

producing microbe itself is not yet understood, but it seems to be possible that metal-chelating agents as 1 can

act as scavenger of trace elements or as detoxifying hgand for high concentrations of heavy metals. Grafe et al.’

investigated the electron spectral properties and the compiex formation with di- or trivalent metal ions of

naturally occurring I and found characteristic bathochromic shifts of the electron spectral pattern.

Our interest was to study the ultraviolet/visible and fluorescence spectra of synthetic I and 2 and to

compare the spectra of their complexes with A13’ ions in ditferent ratios, because, as mentioned above, the TLC

spots of the isomers i and 2 showed characteristic fluorescence under ultraviolet light. Furtheron it was useful to

detect and to identie the l- and 2-N” ion complexes in methanol by UV during the isolation, separation and

purification processes of natural 1 and synthetic 1 and 2.

The ultraviolet/visible spectrum of 1 displays a broad band absorption in the orange-red region (480 to

600 nm) resulting in a violet-blue colour of its methanolic solution. The orange-red coiour of 2 is caused by its

narrower absorption band in the blue yellow region (490 to 515 nm) (Figure 5). The fluorescence emission

spectra of 1 and 2 are clearly discernible- The maximum of 1 ranges near 550 nm (weak emission at 405 nm),

that of 2 near 405 nm (weak emission at 550 nm), when excitated with 305 nm light (Figure 6).

114 W. WERNER et al.

250 300 350 400 450 500 550 600 650 700

wavelength (nm)

Figwe 5 UVir~s-abso~ptiou s~ctta of I and 2

400 450 500 550

wavelength (nm)

16

350 400 450 500 550

wavelength (nm)

Figure 7. ~luorcscence spectra of I-Al~~complcscsformcd b Figure X. Fluorcscencc spectra of 2-AIJ~compleues formed b> addlIon of Al’ ions m molar ratios I :I) (I): I :O.S (2): addrtlon of Al’- ions m molar ratios I .O ( I). I dl.5 1. I (3): I .2 (4). exilation .X)5 run. (2). 1 .I (3). 1:2 (4). cscitalion 3O.i mw

The fluorescence intensities of methanoiic solutions of 1 at 550 nm increases strongly with growing

amounts of Al”’ ions, while the smaller maximum at 410 nm increases less applying the ratios 1:0.5 (2) and 1: 1

(3), but decreases continuing the AISA ions addition to I:2 (4) (Figure 7). In contrary to 1 the isomer 2 fails to

show a fluorescence emission at 530-570 nm, but a very strong fluorescence light is developed while adding

adequately increasing quantities of A13‘ ions (Figure 8, curves l-4). The maximum near 405 nm increases

strongly atier the first addition of Al” ions (curve 2), but then slightly decreases as to be seen in Figure 8 (curves

3 and 4).

Figure 6. Fluoresccncs emission spectra of 1 anil 2 evcltatlon 305 nm.

350 400 450 500 550

wavelength (nm)

Synthesis of tolypocladin and isotolypocladin

EXPERIMENTAL

115

M p.. Euelius M (corr j. TLC Aiunrinmn~ foris (sheets). silica gci 60. F2s-t (Merck) TLC of 1 and 2. Silica gel shccls

(Merck) soaked \%rth 5%, oxalic acrd tn MeOH. drred at room temperature TLC sob I: (l/v). CHCI&le2CO/AcOHIH~0 =

xiZiiitl.6. Sol\. 2.(\i\ j. Mc:COiCHCii-2ii IR spectra. Spzcord iS IR. Carl Zcrss Jena. KBr. Eicctron impact nrass spectra (EIMS).

Jeol JMS-UIOO. UV spectra: Specord 500 UV-VIS (Carl Lerss Jew). Me0H.c: 0 02 mM. P’luorescence spectra: Spectrolluometer

ShM 25 (Konlron lnstrumcnls Inc) I he ‘H NMK (200 MH/) and !‘C NMK (200 MH/) spectra wcrc rccordcd on a Brukcr AC 200-

E spectrometer. DMSOrK solutton unless othenvisc stated. olppml. s: srngict

2-Meth?i-p?_ridine-~.S-tiicarboarlic anhylricic (Jj.- lx. 1 g (100 nmoi) 2-Methvi-p~ridine-i.S-dicarbos~lic acrd

(prcparcd accordrng to rci.!“. m.p. 245-250 “C. dcc.: m p tound 210-2x0 OC’. dcc.) arc rclluscd .3tl mm m 150 mL acctrc anhydrrde.

co&d. lhc small residue is rcmo\cd and lhc liltraic cbaporated 15.5 g (Y5oioj bright cr~stais. in p. 102-103 “C (CHCIr). Anal.

found: c‘. 5x 71: H. .i.LS: N. X.7Y Calc for CxHGN03 (IO.% I). C. 5x.YO. H. 1OY. N. X iY IK. IX60 and 17X6 cm’ (anhyirrdc). ‘H

NMK h=‘J Ii (s.H-6). 7.7O(s.H-7).275(s.C‘H1) ‘?C NMK 167.5. Ihl 3. Ihl.0. I-h,.5.,13xY. 122.3. 117.7.25.2(C’H&

f~-Mcth!I-J-(2,~,S-trimcthor~-benzu?_l)-nicotinic acid (6) - In a three ncckcd bottle are placed 6-t g (-IX mmol) anhydrous

alunnnium chiuridc and suspended \\rth -iii mi water-fret nuih> lcw chloride The nn~turc rs rtrrrcd and cooled at abuut 5 ^C and

l\\o separate soiulrons oi 2 6 g ( I6 mmol) 4 (tn 25 mL meth!lenc chlortde) and X I g (4X mmol) commercially avatlabic 1.2.1-

lrltlrcilro\~-bcrr/crrc (m 25 mL mclh~ienc ciriorrdc) arc added durmg 15 min b! each lwo dropping funncis. Let 111~. lcn~p.ralurc rise

lo I5 “C durmg 15 mm and strr 2 h al room lcmperature ‘l‘hc red-brown rcsmous mass rs then decomposed b\ rcc and cont. HCI

(2 i) under strrrmg and rcc water cooiinx from uutsidc. From lhc rcsul~mg !cllw soiulnm a microqstallinc prccipitalc scparatcs.

\\htch is cctmigcd. The water phase rs decanted and the solids arc sucked ofi. A further crop can be isolated irom the aqueous

filtrate. The ~rcld amounts to A.5 g (75% j 6-ir?ciroclrloridc-irclrrilr!dratc. m. p. 2.33-236 “C (diluted HCI). Amai. fuund. C. 5l2X. H.

5.35: Cl. itr ()I: N. 3 711 Caicd for C,H-NO6 HCi 0.5 H20 (376.x) C. 54 IY. H. 5 (IX: Cl. Y.41. N. 3.72. Water. found 1.76

ialcd. 24 MS m/c= .i.il i (M’) C‘alcd forC’~H,-NO,,((J.iI 3) IK IO.i~and 171-tcmr ! H NMK: (Numbermg set schcmc 2) o =

X.YJ (s. H-6). 7 3Y (s. H-3). 7 3 I IS. H-h’). 6.6X (s. H-3’). 3 X7 and 3 7X (s. CHJO-2’. s. CHIO-J’). 3.~ (s. CHIO-5’). 2.~ (s. CHI-2).

The 6-ir?drucirioridc-l1~rlrrll!dralc rs dissol\cd m ualcr. adjuslcd Hith a sodium ucclalc soluliun lu pH 6 and colourlcs crystals arc

prccrprtatcd: M. p. 250-25 I “C (nalcr). Kf = (I 53 (sob. I ). .4nal found: C. 6 I Si: H. 5.2 I: N. .I I6 Calcd. for Cr-H,-NO, (33 I .3),

C. 61.61: H. 5 17: N. 4 2-i MS. mfc = i-3 I 2 (M ’ ) C‘alcd. m = 33 I 3 IK: 163x and 1707 cm-’ (COOH. CO). ‘H NMK. ci = X Y2 (s.

H-6). 7. 3X (s. H-3). 7 IO (s. H-6’). 6.67 (s. H-3’). 3 x7 and 3.7~ (s. CHIO-2’. s. CH@-1’). 3.3X (s. CHTO-5’). 2.53 (s. CH3-2)

6-Meth?l-~-(2,1,5-trimeth~~~-b~n~~i)-nic~tini~ acid i7j: 2.08 g HgCiZ (7.6 mmol) dissolved in 30 mL \latcr arc gtvcn to

20 X g (.i I7 mmol) Ln dust. I mL cont. HCI rs added under shakmg. and the mtsturc IS decanted aflcr 5 mm. I.66 g (5 mmol) 01 ~hc

kc10 acid 6 is solwzd in diluted h~drochiorrc drid (27.5 mL water/ 4.14 mL. cont. HCI). and the mi~lure is put b> stirrtng to the Zn

amalgam I he rcductron starts al once. and after 30 mm the process IS fnushcd (‘fLC). After 2.5 h the tillratc IS evaporated the

resrdue. suspended in I5 mL water. is solved m ammonia and H?S gas introduced until1 all ZnS is precipitated. The misturc is

hcatcd for I h to facrhtatc the folloumg tillratron I’hc ftltratc IS e\aporatcd. the rcsrduc dtssolved m 30 mL hot water and acrdtticd

Hith acetic acid (20%) to ihc rsoelectrrr point. \+hcrc 1.5 g 7 (91%) ct~stallizc. colourless prisms. m. p. 1.5X-159 “C. P.- 0.33 (solv.

116 W. WERNER et al.

I). Anal. found: C. 64.31: H, 6.12; N, 4.47. Calcd. for C1,H19N05 (317.3): C. 64.34: H, 6.03; N. 4.41. MS: m/e found 3 17.2. c&d.

317.1247. IR: 3430. 2990. 2830. 1618. 1508,13Y5. ‘H NMR: (Numknng see scheme 2) fi = 8.77 (s. H-6). 6.86 (s, H-3). 6.76 (s. H-

6’), 6.68 (s. H-3’). 4.18 (s. CH:), 3.77. 3.69, 3.63 (3 s, OCH1). 2.39 (s, CH1-2).

Z-Methyl-S-(2,4,5-trimethoxy-hen~uyl)-isonicotinic acid (J). The isomer 5 is enriched in all acid filtrales resulling from

the isolation and purification of the described Isomer 6. By fractionated precipitation with sodium acetate solution colorless crystals

are separated. The yield of 5 amounls lo 0.9 g (17%) , m. p. 286-287 “C (dec.) (water); RF= 0.4 (solv. 1). Anal. found: C. 60.98: H,

5.16; N. 4.32. Calcd. for C17H1,NOh (331.3): C. 61.63: H. 5.17: N. 4.23. MS: m/e found 331.2. calcd. 331.1057. ‘H NMR:

(Numbering see scheme I), pyridine ring. 6 - 8.36 (s. H-6). 7.60 (s. H-3). 2.58 (s, CH1-2); bemene ring. 6 = 7.32 (s, H-6). 6.67 (s,

H-3). 3.87 and 3.76 (s, CH@-2, s. CHQ4). 3.43 (s. CHQS).

3-Methyl-5,7,&trihydroxy-2-aza-anthraquinone-(9,10) (2). 33 1 mg (I mmol) 6 is heated in 5 mL cont. sulfuric acid to

120 “C dunng 2 h. After coohng the solution is put on Ice The most of the acid IS neutralized wilh sodmm hydr0xu.k solution. the

rest finally adjusted with sodium acetate to the pH value 6. Then the product is extracted fully with chloroform. the orange red

cstract dr~cd with sodmm sulfate. and the filtrate 1s cvaporaled. The vieId amounts ca. 150 mg (55%) rmcrocrystalhnc red powder.

which crystallizes somelimes in dark red solids from chloroform. During heating from 230 to 260 “C long red crystals are generated.

m. p. 3 17 “C (dcc.). sublimation 230-260 “C. vermilhon powder. Rf= 0.6 (sol\ 2). Anal. found: C. 61.6’); H. 3.42: N. 5.13. Calcd.

for C14H9NOP (271.2). C. 62.00. H, 3.35, N. 5.16. MS. m/e found 271.0451. calc.271.0481. IR. 3425. 3000, 2600. 1623. 1586. 1145

cm~‘. ‘H NMR: 6 = 13.18 (s. 2 OH). 9.19 (s. H-l). 7.82 (s. H-4). 6.5’) (s. H-7). 2.68 (s, CH,). “C NMR : 2468 (CH?). 105.75.

109.36. 112.14. 117.53. 123.63. 139.18. 148.00. 149.50. 158.20. 161.09. 16.5 57. 181.96 (CO). 186.09 (CO).

X ray dffraction: CIqHzINOr. M, = 271.2. orthorhomhc. Plxa. a = 13.428 (3). b = 7.696 (2). c = 2 1.5.22 (4). A V = 2224. I (Y) A’.

Z = 8. D, = 1.6210 Mg m ‘, i, (MO Ku) = 0.71073 A. p = 0.125 mm !, F(OOO) = 1120. T = 193 K. R = O.fb76 (I > 20(I). wR = 0.19Y

for all 2674 unique diffractometer data.- Crystalhzat~on succeeded from CHCI,. One c@al of the dimensions 0.48 * 0.2X * 0.01

mm3 was sealed in a Lindemann-gJas capillary. 25 reflections with 9 > 5” were used to determine the cell parameters on a four

ctrclc computer controlled diffractometer (R3m/V Siemens). The mtcnsnies were measured on the same apparatus: MoKtx ra&ation.

9 max < 28”. 323Y reflections (-2 ‘. h 17. -10 ’ k ’ IO, -28 ’ 1 ’ ). of which 2474 were unique. which were used for the structure

analysis. Direct methods for solving the phase problem (Shrldrick. 1990). rctinement of the slructure paramelrrs by kdSk%pmS

Methods (full-matrix minimization of ( / F. / ’ - 1 F. / ’ )* weighting scheme: w = l/o’ (F) according to the counting statistics. 185

parameters. coordinates of the H atoms were got by geometrical considerations, S = 0.85. R = 0.076 (1 > 2 CT (I)), R,, = 0.199 (all

data), 10 largest peaks in the difference map. All calculations were made by a microVAX II with the SHELXTL-PLUS. SHELXS

and SHELXL programs (Sheldrick. IYY0,1YY3).Y The results are given m the figures and the tables. wtuch are avadable as

Supplementary Material.*

3-Methyl-S,7,8-triacetoxy-2-aza-anthraquinone-(9,10) (2b): 270 mg (1 mmol) of 2 in a solution of 30 ml_ acetic

anhydride and 3 mL pyridine are heated 30 min to 100 “C The dark red mixture clears to a yellow brown solulion. After cooling

yellow crystals separate, and they are collected. Together with a further crop from the filtrate the yield amounts 330 mg of 2b (83%).

m.p. 210-211 “C (ethyl acetale). Rf = 0.9 (solo. 1). Anal. found, C. 60.29. H. 3.82; N. 3.69. Calcd. for C2,,H,sN9, (397.3): C.

60.46: H. 3.80; N. 3.53. MS: m/e found 397.2, calcd. 3Y7.07870 (M+). ‘H Nh4R (CDC13): Y.31 (s, H-l), 7.80 (s, H-4). 7.41 (s, H-6).

2.76 (s. CH?3). 2.49. 2.47. 2.36 (3 s. CH&OO).

Synthesis of tolypocladin and isotolypocladin 117

J-Methyl-S,6,S-trihydroxy-2-aza-anthraquinone-(9,10) (1): The proccdurc IS the same as described above for 2 The

crystals look reddish brown after sublimation in vawo (230-260 “C. 67 Pa). or dark violet if rccrystaliized from CHCI, / EIOAc. The

ycld amounts 4X?& of the thcoly: m. p. >3t)O ‘C (dec.) jrcf.’ m. p. >320 OC’ (dcc.)l. Rf = 0.6 (solv. 2). MS: m/c found 271.0472

(M’). calcd. 271.0481. Anal. found: C. 61.X0: H. 3.6.5: N. S.20. Calcd. for C,,HsNOq (271.2): C. 62.00: H. 3.3.5: N. S.lh.- IR:

301,O. 2YtjS (broad). 1023 (CO). 15855 (CO). 1456. 1412. 13lIY (max.). I1 IX. 92X. 763. ‘H NMR: 2.72 (s, CH3). 6.74 (s. H-7). 7.7Y

(s. HA). Y.2Y (s. H-l). 11.80 (broad). 12.80 (broad). 13.33 (s. H-6). “C NMK: 24.7 (CH3). 105.0. 110.3. 113.0. 117.6, 124.2. 138.3.

I-18.0. 149.7. 357.3. 160.S. 164.‘). 183.0 (CO). 186.0 (CO).

3-Methyl-5,6,8-triacctox~-2-aza-anthraquinone-(9,10) (lb): I mmol I IS acylated tn the same manner as dcscr~bed for 2.

The yield amounts 0.3s g (88%). purdication b! column chromatogaph! (v/i. CHCI? / Me?CO = Y/l) or recnstalliration. yellow

crystals. m. p. 217-21Y OC (ethyl acetate). Kf 0.Y (solv. I ). Anal. found: C. 60 31: H. 3.YO: N 3.X0. Calcd for C’,,ti~,Nt& (3’97.3)

C. 60.46: H. 3.80: N. 3 53. MS: m/c found 3Y7.2. calcd. 3Y7 0788Y (M’). ‘H NMK (CDCI?): Y.32 (s. H-l). 7.76 (s. H-4). 7.42 (s. H-

6). 2.74 (s. CH3-3). 2 48. 2.47. 2.35 (3 s. CHICOO). “C NMR (CDCI1): 181.05 (CO). 179.99 (CO). 168.92. 167.96. l66.YX. 165.56.

149.38. 148.6’). 148.53. 140 il. 138.35. 127.05. 12565. 123.9’). 123.09. 117.7’). 77.63. 76.99. 76.3.5. 25.16 (CHI).

Acknowledgements

This publication is one of the results of the Bh4FT-Project No. 03 10278A (1992), financed by the

Hlr,rdrsmiilr.slrr~ir I~iwschmg und khndo~ie, Bonn, BE0 jiilich, Germany.- We are gratehi to Mrs. Gabriele

Gtinther, IMB, for her technical assistance

REFERENCES AND NO’IXS

I

2.

3.

4.

>.

6.

7.

8.

Griifc. U., Ihn. W . Txwlt. D.. Miosga. N.; Kaden. U.. SLhlcgcl. B.. Bornyann. E.-J.. Scdmera. P.. Novak. J Hwl. .\k/rr/.v

1990, 3. 39-44.

Arscnauit. G. P.. l’rrrc~hr&w~ Ixll. 1965. J_i. J043-iOi7

Cameron. D. W.: Deutscher. K. R.: Feutnll. G. 1.: 7rlmhr&w Ltvf.. 1980. ?I. SOXY-SOYO.

Cameron. D. W.: Deutschcr. K. R.: Fcutrill. G. 1.: .iu.w J. (‘hem. 1982. 3.5. 143Y-l-&SO.

Cameron. D. W.: Deutscher. K. R.: Feutrill. G. 1.; Hunt. D. E.::lr~sr. .I U~I. 1982. 35. IlSl-1461.

Watanabe. M.. Shin&a. E.. Shiml/.u. Y.. Furukuwa. S.. It/&edwz 1987.13. 5281-5286.

Wcmer. W.: Grafe. U.. (~/tenleRungsschrIJi DE 42 3 I 632 A I. 22.9.92/24.3.Y4.

Shcldrick. G. M.. University of Giittingen 1990. SHELXTL-PLUS. an integrated syslcm for solving. relining and

drsplayng crystal structures from &tfractlon data. SHELXS-Ytl. F’oK1‘RAN-77 program for the solution ol‘ crystal

structures from X-rat or neutron diffrxtion data. 1993 SHELXZ-93. a FORTRAN-77 program for the refinement of crystal

structures from diffraction data. X ray diffraction data: Lists of the anisotropic diplacement parameters. of bond lengths and

bond an&s of H a(om coordinates and of the structure factors have been depo&d with the British Library, Len&g

Dwision. The atonnc co-ordinates tor this work are avatlable on request from the Dtrector of the Cambridge

118 W. WERNER et al.

Y.

IO.

Cr~slallographic Data Ccnlrc. University Chemical Laboratory. Lcn&id Rod. Cambridge CB2 IEW. Any rqucsl kndd

be accompamed by the full literature citation for this commumcatlon.

Mcdcnlsw. A.C.. Vankuno. V. P . Akimcnko. V K.. MioLh/,r/,w 1989 54. 6iY-628.

‘lhm. H.. la/i~:yyok~ kzsshr 1991. XI. 141-143 (lap.). ( ‘hew f’hnr~r HUN /'/i&w/. 1YSY. 7. Y30 (Engl.). C.A. 1961.

SS. illSOd.

(Received in Germany I I December 1995; revised 16 October 1996; accepted 17 October 1996)