Synthesis of thiaazaheterocycle nucleoside analogues

Article abstract of DOI:10.1081/NCN-120006829

The syntheses of thiazinone, thiazinedione and thiazolinone base modified nucleoside analogues have been discussed in both the deoxy- and ribosyl series. Both inter- and intramolecular N-glycosylations were evaluated.

Full text of DOI:10.1081/NCN-120006829

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SYNTHESIS OF THIAAZAHETEROCYCLE NUCLEOSIDE
ANALOGUES
A. Ané a , G. Prestat b , M. Thiam b , S. Josse b , M. Pipelier b , J. P. Pradère b & D. Dubreuil c
a Laboratoire de Chimie Organique Structurale , Abidjan 22, 22 BP 582, Côte d'Ivoire
b Laboratoire de Synthèse Organique , UMR au CNRS 6513, 2 rue de la Houssinière, 44322
Nantes 3, BP 92208, France
c Laboratoire de Synthèse Organique , UMR au CNRS 6513, 2 rue de la Houssinière, 44322
Nantes 3, BP 92208, France
Published online: 31 Aug 2006.
To cite this article: A. Ané , G. Prestat , M. Thiam , S. Josse , M. Pipelier , J. P. Pradère & D. Dubreuil (2002) SYNTHESIS OF
THIAAZAHETEROCYCLE NUCLEOSIDE ANALOGUES, Nucleosides, Nucleotides and Nucleic Acids, 21:4-5, 335-360, DOI: 10.1081/
NCN-120006829
To link to this article: http://dx.doi.org/10.1081/NCN-120006829
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MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS, 21B4&5), 335±360 B2002)
SYNTHESIS OF THIAAZAHETEROCYCLE
NUCLEOSIDE ANALOGUES
A. Ane,1 G. Prestat,3 M. Thiam,2 S. Josse,3 M. Pipelier,3
J. P. Pradere,3 and D. Dubreuil3,*
1Laboratoire de Chimie Organique Structurale, Faculte des
Sciences et des Techniques, 22 BP 582 Abidjan 22, Cote d'Ivoire
2Laboratoire de Synthese Organique, Faculte des Sciences et des
Techniques, Universite Cheikh Anta Diop, BP 5005 Dakar-Fann,
Senegal
3Laboratoire de Synthese Organique, UMR au CNRS 6513,
Faculte des Sciences et des Techniques, 2 rue de la Houssiniere,
BP 92208, 44322 Nantes 3, France
ABSTRACT
The syntheses of thiazinone, thiazinedione and thiazolinone base mod-
i®ed nucleoside analogues have been discussed in both the deoxy- and
ribosyl series. Both inter- and intramolecular N-glycosylations were
evaluated.
In recent years, the search to discover potent and selective antiviral or
anticancer agents has resulted in the design of nucleoside analogues with
modi®cations on the heterocyclic aglycone moiety. Some examples have
shown that the structure of the nucleobase can be changed considerably while
retaining the biological interest.[1] In particular, N-[2] and C-[3]linked nucleo-
sides tethered to ®ve and six membered modi®ed azaheterocycles exhibiting
biological activity have aroused new attention. We proposed the synthesis
of nucleosides incorporating novel thiaazaheterocycles having structural
analogies with the natural nucleobases. Modi®ed 30-thiaazaheterocycle
*Corresponding author.
335
Copyright # 2002 by Marcel Dekker, Inc.
www.dekker.com

336
ANE ET AL.
nucleoside analogues have been already synthetized from 30-thiaazabutadiene
thymidine precursors.[4] Here, the elaboration of N-deoxy- and N-ribonu-
cleosides has been investigated by N-glycosylation with thiazinone, thiazine-
dione and thiazolinone heterocycles. An intramolecular glycosylation process
was also attempted to achieve stereoselectivity with the N-deoxyribosyl
analogues.
The preparation of thiaazaheterocycle analogues can be achieved from
4-dimethylamino-1-thia-3-aza-but-1,3-dienes BN-thioacylamidine) or from
their thiocarbamate intermediates.[5] 6-Methoxycarbonyl-1,3-thiazin-2,4-
dione 3 was prepared from the dithiocarbamate 1 BSch. 1). [3 ‡ 3] Cycload-
dition of 1a and 1b with dimethyl acetylenedicarboxylate gave the corre-
sponding thiazinones 2a and 2b in 90% and 78% yield, respectively.
Hydrolysis of the imines 2a±b using p-toluensulfonic acid in acetone a€orded
the thiazin-2,4-dione 3 B80%).
The 5-acetyl-3,6-dihydro-1,3-thiazin-2-one 6 was synthesized from the
thiaazabutadienes 4a and 4b. Condensation of thiocarbamates 1a and 1b
with N, N-dimethylformamide dimethylacetal leads to the formation of
thiaazabutadienes 4a B83%) and 4b B90%) respectively, which a€orded the
thiazines 5a B66%) and 5b B77%) upon [4 ‡ 2] cycloaddition with methyl
vinyl ketone. Hydrolysis of these thiazines with p-TSAgave the targeted
thiazin-2-one 6 in 70% yield.
Scheme 1.

THIAAZAHETEROCYCLE NUCLEOSIDE ANALOGUES
337
Scheme 2.
The synthesis of 4-methyl 2H-1,3-thiazolin-2-one 11 was achieved from
2-ethoxy-4-methyl-N-thioacylamidine 8 BSch. 2). Condensation of ethyl-
thiocarbamate 7 with N,N-dimethylacetamide dimethylacetal a€orded the N-
thioacylamidine 8, in quantitative yield, and furnished the thiazol-2-ine 9
upon [4 ‡ 1] heterocyclisation with the trimethyl sulphonium ylide,[5e] in 40%
yield. Addition of methyl iodide resulted in quantitative aromatisation of
compound 9 to form thiazole 10 which was converted to the target thiazo-
linone 11[6] B80%) by treatment with phosphorus tribromide B10 remains
stable under usual acidic hydrolysis).
The yield of thiazole 10 was improved by an alternate route via the
thiazoline 12. The reaction of the thiocarbamate 7 with chloroacetone gave
the thiazoline 12, in 75% yield, which was quantitatively transformed into
the thiazole 10 in re¯uxing toluene.
The nucleoside derivatives were synthesized from two haloribosyl pre-
cursors: 3,5-di-O-benzoyl-2-deoxy-ribofuranosyl chloride[7] 13 and 5-O-tert-
butyldiphenylsilyl-2,3-O-isopropylidene-ribofuranosyl chloride[8] 28, chosen
as glycosyl donors. N-Glycosylations with deoxyribosyl chloride 13 and
thiaazanucleobase analogues 3, 6 and 11 were ®rstly attempted in the pre-
sence of DBU B1.1 eq.) leading to the corresponding deoxynucleosides 14

338
ANE ET AL.
Scheme 3.
B75%), 15 B75%) and 16 B20%), respectively BSch. 3). Anomeric deoxy-
nucleosides 14 and 15 were isolated in 1:1 and 2:1, a:b ratio, respectively,
whereas, thiazolinone analogue 16 was obtained in 9:1, a:b ratio.
Attempts to remove the p-chlorobenzoyl group in thiazinone deoxy-
nucleosides 14 and 15 under basic conditions induced partial degradation
leading to ring opening of the heterocycle moiety. Treatment of 14b and 15b
with catalytic amount of MeONa a€orded the formation of anomeric mix-
ture of N-amidoacetylenic ribosyl 17 B95%) and N-carbamate ribosyl 18
B60%), respectively. However, no such degradation was observed with thia-
zolone 16b which on treating with KOH gave the desired deoxynucleoside
19b B80%).
The results obtained in the deoxynucleoside series prompted us to
investigate an alternative strategy involving a stereoselective intramolecular
transposition.[9] Following this hypothesis, the primary target appeared to be
the elaboration of the thiaazaheterocycles at the 50-position of a deoxyribo-
side precursor BSch. 4).

THIAAZAHETEROCYCLE NUCLEOSIDE ANALOGUES
339
Scheme 4.
Methyl 30-tert-butyldiphenylsilyl-50-thiocarbamate-deoxyriboside 21
was prepared from methyl 30-tert-butyldiphenylsilyl-deoxyriboside 20 in
95% yield. Following a similar protocol as mentioned in the synthesis of
N-thioacylamidines BSch. 2), reaction of thiocarbamate deoxyriboside 21
with N,N-dimethylformamide dimethylacetal and N, N-dimethylacetamide
dimethylacetal, led to the 50-thiaazabutadienes 22a and 22b, in 95%
yields. The 50-thiaazaheterocycle isodeoxynucleosides 23 B70%), 24
B80%) and 25 B50%), were formed by cycloaddition reactions as pre-
viously discussed from the thiocarbamate 21 and from the dienes 22a
and 22b, respectively.

340
ANE ET AL.
Attempts to achieve the 50,10-transposition of 50-thiazinone deoxyribo-
sides 23 and 24 using various Lewis acids[9] resulted in the hydrolysis of the
imine function without occurrence of N-glycosylation. However, partial
success was achieved with 50-thiazole deoxyriboside 25 using silyl tri¯ates
initiating an intramolecular rearrangement. Thiazole deoxyriboside 25 was
treated twice with tert-butyldimethylsilyl tri¯uoromethanesulfonate B2.2 eq)
along with supplementary amount of tert-butyldiphenylsilyl chloride B2 eq).
Subsequent hydrolysis of the anhydroammonium intermediate with sodium
carbonate competitively gave the desired b-deoxynucleoside 26 B20%) along
with ribofuranose 27 B20%) and unreacted starting material 25 B41%). The
use of a higher amount of catalysts improved the yield of the furanose 27.
Unfortunately no improvement in the transposition process was observed
using other catalysts. Due to the nature of the thiaazaheterocycle change of
the anomeric group by a more labile thioether activating group is either not
suitable. However, the deoxynucleoside 26 was isolated as a single diaster-
eoisomer and its b-con®guration was con®rmed by nOe experiment.[10]
Finally, the deprotection of compound 26 in the presence of tetra-
butylammonium ¯uoride led to the desired deoxynucleoside 19b in 95%
yield.
The synthesis of nucleoside analogues was then extended to the ribo-
nucleosides. N-Glycosylations of the ribofuranosyl chloride 28 with hetero-
cycles 3, 6 and 11 in the presence of DBU B1.1 eq.) led to a mixture of
corresponding anomeric nucleosides 29 B54%, a:b ratio: 1=1), 30 B50%, a:b
ratio: 1=3) and 31 B47%, a:b ratio: 1=2), respectively BSch. 5).
Deprotection of nucleoside analogues 29 Bmixture) and puri®ed thiazole
anomers 31a and 31b was carried out in two steps: i) treatment of 29 with p-
TSA to get the a- and b-ribosyls 32a and 32b B60%), which were isolated in
1:1 a:b ratio, and treatment of 31 with tetrabutylammonium ¯uoride to get
the corresponding 50-OH intermediates 35a and 35b B70%) BTBAF induce
degradation in case of 29). ii) Hydrolysis of the ketal group in 32a, 32b, 35a
‡
and 35b with Dowex H resin to get the free nucleosides 33a, 33b, 36a and
36b in 65% yield. Treatment of anomeric mixture of 30 was carried out
without puri®cation following a similar procedure to a€ord an a,b-anomeric
mixture of the corresponding free nucleoside 34 in 44% overall yield Ba:b
ratio 1:3).
In conclusion, we have designed the synthesis of thiaazaheterocycle
base modi®ed nucleoside analogues in both deoxy- and ribofuranosyl
series. N-Glycosylation between halogenofuranosyls and thiaazahetero-
cycles seems to be the most ecient process to produce corresponding
nucleoside derivatives. Nevertheless, intermolecular stereoselective glyco-
sylation remains attractive for the stereoselective synthesis of deoxy-
ribonucleosides. No signi®cant antiviral activity of these nucleoside
analogues measured on CEM4 lymphocytic cell lines infected with HIV-1
BLai strain) has been observed.

THIAAZAHETEROCYCLE NUCLEOSIDE ANALOGUES
341
Scheme 5.
Experimental Data
1H and 13C spectra were obtained on Bruker ARX 400 or Bruker
AC200. Chemical shifts Bd) are given in ppm relative to the TMS Btetra-
methylsilane). The 1H-1H coupling constants BJ) were measured in Hz. Mass
spectra were recorded on a HP 5889 A quad spectrometer or a ZabSpecE-
TOF spectrometer for high resolution spectra. Infrared spectra were recorded
on a Bruker IFS 45 WHR spectrometer Melting points were determined with
a RCH BC. Reichert) melting point apparatus. Speci®c rotations were

342
ANE ET AL.
measured at 20ꢀC using a Polar 341 Perkin-Elmer. Thin layer chromato-
graphy were performed on Merck 60 F254 coated plates. Silica gel chroma-
tography were performed with 0.04±0.06 mm silica gel. All the solvents were
puri®ed using standard procedures.[11]
6-Methoxycarbonyl-2-methylthio-4H-1,3-thiazin-4-one 82a) and 2-Benzyl-
thio-6-methoxycarbonyl-4H-1,3-thiazin-4-one 82b). General procedure. To a
solution of thiocarbamate 1a ^ b B10.91 mmol) in ethanol, dimethyl acet-
ylenedicarboxylate B1.6 mL, 13.09 mmol) was added with stirring, stirring
was continued 1 h at room temperature. The product was isolated by ®l-
tration and washed with ethanol. The crude solid was recrystallized from
1
ethanol to get 2a±b. ꢀ2a) 90% yield: m.p. 140±141ꢀC. H NMRBCDCl3;
200 MHz) d: 2.85 Bs, 3H); 3.87 Bs, 3H); 6.96 Bs, 1H, H5). 13C NMR BCDCl3;
50 MHz) d: 16.3 BCH3S); 52.9 BCH3O); 120 BC-5); 144.2 BC-6); 166 BCˆO
‡
ester); 177.9 BC-2); 199.98BC-4). MS BEI) M =z B%): M ˆ 217; 203 B82); 144
B70); 116 B100); 86 B70); 57 B55). I.R. KBr Bm cmÀ1) 1702; 1458; 1337; 1213;
1
1002. B2b) 78% yield: m.p. 106±107ꢀC. H NMR BCDCl3; 200 MHz) d: 3.86
Bs, 3H); 4.68Bs, 2H); 6.98Bs, 1H, H5); 7.37 Bm, 5H, HAr). 13C NMR BCDCl3;
50 MHz) d: 38.2 BCH2S); 52.9 BCH3O); 120.2 BC-5); 128.3 to 134.3 BC-Ar);
144.0 BC-6); 166.0 BCˆO ester); 177.9 BC-2); 196.7 BC-4). MS BEI) M=z B%):
‡
M ˆ 293; 116 B29); 91 B100); 65 B38). I.R. KBr Bm cmÀ1) 1717; 1686; 1462;
1332; 1209; 1160; 1004; 719.
6-Methoxycarbonyl-4H-1,3-thiazin-2,4-dione 83). To a solution of 2a^c
B3.41 mmol) in acetone B30 mL) was added p-toluene sulfonic acid mono-
hydrate B0.65 g, 3.41 mmol). The mixture was stirred for 6 h at room tem-
perature, 100 mL of water and 100 mL of ethyl acetate were added. After
extraction, the organic layer was washed with brine, dried over magnesium
sulfate, ®ltered and then evaporated to dryness. The product was puri®ed by
¯ash chromatography on silica gel eluting with petroleum ether=ethyl acetate
B8=2) and recrystallized from dichloromethane to get 3 in 80% yield. m.p.
1
168±169ꢀC. H NMR Bacetone-d6; 200 MHz) d: 3.85 Bs, 3H); 6.87 Bs, 1H);
11.34 BNH). 13C NMR Bacetone-d6; 50 MHz) d: 53 BCH3O); 118.3 BC-5);
143.7 BC-6); 166.1 BCˆO ester); 166.4 BC-4); 169.3 BC-2). MS BEI) M=z B%):
‡
M ˆ 187 B32); 144 B63); 116 B84); 86 B45); 85 B100); 59 B45); 57 B83); 49 B25).
I.R. KBr Bm cmÀ1) 3209; 1761; 1721; 1677; 1339; 1220. Anal. Calcd for
C6H5NO4S: C, 38.50; H, 2.69; N, 7.48; S, 17.13. Found: C, 38.43; H, 2.80; N,
7.33; S, 17.09.
4-N,N-dimethylamino-2-methylthio-1-thia-3-aza-1,3-butadiene 84a). N, N-
dimethylformamide dimethyl acetal B2.12 mL, 16 mmol) was added to the
thiocarbamate 1a B1.71 g, 16 mmol). The mixture was stirred for 1 h at room
temperature. After removal of the methanol formed, the crude product was
puri®ed by ¯ash chromatography on silica gel eluting with petroleum

THIAAZAHETEROCYCLE NUCLEOSIDE ANALOGUES
343
1
ether=ethyl acetate B8=2) to get 4a in 83% yield. m.p. 83±84ꢀC. H NMR
BCDCl3; 200 MHz) d: 2.6 Bs, 3H, CH3S); 3.17, 3.24 2*Bs, 3H, NBCH3)2); 8.68
Bs,1H, H4). 13C NMR BCDCl3; 50 MHz) d: 36.1 BNBCH3)2); 41.7 BCH3S);
‡
156.9 BC-4); 220.99 BCˆS). MS BEI) M=z B%): M ˆ 162; 115 B100); 99 B23);
71 B44); 44 B40); 42 B50). I.R. KBr Bm cmÀ1) 1619; 1412; 1313; 1260; 1204;
1121; 983; 951.
2-Benzylthio-4-N,N-dimethylamino-1-thia-3-aza-1,3-butadiene 84b). Same
experimental conditions as described for 4a, starting from thiocarbamate 1b
1
gave 4b in 90% yield. m.p. 93±94ꢀC. H NMR BCDCl3; 200 MHz) d: 3.09,
3.12 2*Bs, 3H, NBCH3)2); 4.47 Bs, 2H, CH2S); 7.237.32 Bm, 5H, HAr); 8.62
Bs,1H, H4). 13C NMR BCDCl3; 50 MHz) d: 36.1 BCH2S); 40.0, 40.6
BNBCH3)2); 126.8to 137 BC-Ar); 157.2 BC-4); 218.6 BC ˆS). MS BEI) M=z B%):
‡
M ˆ 238; 115 B100); 99 B21); 91 B33). I.R. KBr Bm cmÀ1) 1635; 1624; 1472;
1344; 1338; 960; 723.
5-Acetyl-2-methylthio-6H-1,3-thiazine 85a). N-thioacylamidine 4a B3 g,
18.49 mmol) was heated with methyl vinyl ketone B15 mL, 184.7 mmol) at
65ꢀC for 72 h. After removal of the solvent in vacuo, the crude product was
puri®ed by ¯ash chromatography on silica gel, eluting with petroleum
1
ether=ethyl acetate B8=2), to get 5a in 66% yield. m.p. 66ꢀC. H NMR
BCDCl3; 200 MHz) d: 2.39 Bs, 3H, CH3S); 2.57 Bs, 3H, CH3); 3.60 Bs, 2H,H-6);
7.71 Bs, 1H, H4). 13C NMR BCDCl3; 50 MHz) d: 14.5 BCH3); 22.2 BCH2S); 25
BCH3S); 115.8BC-5); 145 BC-4); 170.1 BC-2); 195.5 BC ˆO). MS BEI) M=z B%):
‡
M ˆ 187; 145 B90), 144 B29), 71 B17), 43 B100); 39 B15), 28 B30).
5-Acetyl-2-benzylthio-6H-1,3-thiazine 85b). Same experimental condi-
tions as described for 5a, starting from thiocarbamate 4b gave 5b in 77%
yield. m.p. 86±87ꢀC. 1H NMR BCDCl3; 200 MHz) d: 2.39 Bs, 3H); 3.6 Bs, C-6);
4.43 Bs, 2H, CH2S); 7.37±7.33 Bm, 5H, HAr); 7.86 Bs, 1H, H4). 13C NMR
BCDCl3; 50 MHz) d: 22.6 BCH3); 25.4 BC-6); 36.1 BCH2S); 116.1 BC-5); 127.6
to 136.2 BC-Ar); 145.97 BC-4); 160.6 BC-2); 195.9 BCˆO). MS BEI) M=z B%):
‡
M ˆ 263; 123 B15), 91 B66), 71 B62), 65 B18), 43 B100), 42 B40), 41 B42), 39 B23),
31 B22), 29 B39), 27 B27).
5-Acetyl-3,6-dihydro-2H-1,3-thiazin-2-one 86). Same experimental
conditions as described for 3, starting from 5a±b gave 6 in 70% yield. m.p.
159±160ꢀC. 1H NMR Bacetone-d6; 200 MHz) d: 2.3 Bs, 3H); 3.88 Bs, 2H); 7.52
Bs, 1H, H4); 9.32 BNH). 13C NMR Bacetone-d6; 50 MHz) d: 24.8BCH 3); 112.6
‡
BC-5); 139.5 BC-4); 167.6 BC-2); 194.4 BCˆO). MS BEI) M=z B%): M ˆ 157;
115 B16); 86 B14); 82 B24); 70 B18); 55 B69); 54 B53); 43 B100); 39 B16); 28 B51).
I.R. KBr Bm cmÀ1) 3226; 3084; 1685; 1626; 1305; 1204. Anal. Calcd for
C6H5NO2S: C, 45.85; H, 4.49; N, 8.91; S, 20.40. Found: C, 45.74; H, 4.44; N,
9.05; S, 20.69.

344
ANE ET AL.
2-Ethoxy-4-methyl-4-8N,N-dimethylamino)-1-thia-3-aza-1,3-butadiene 88).
N,N-dimethylacetamide dimethyl acetal B2.33 mL, 16 mmol) and thiocarba-
mate 7 B1.68g, 16 mmol) were stirred for 1h at room temperature. After
removal of the methanol under vacuo, the crude product was puri®ed by ¯ash
chromatography on silica gel, eluting with petroleum ether=ethyl acetate
1
B8=2), to get 8 in quantitative yield. H NMR BCDCl3; 200 MHz) d: 1.36 Bt,
3H, CH3-CH2, J ˆ 7.10); 2.43 Bs, 3H, CH3); 3.12, 3.15 2*Bs, 3H, NBCH3)2);
4.40 Bq, 2H, CH2-CH3, J ˆ 7.10). 13C NMR BCDCl3; 50 MHz) d: 14.0 BCH3-
CH2); 17.4 BC4-CH3); 38.4, 38.7 BNBCH3)2); 66.5 BCH2); 164.9 BC-4); 196.6
BCˆS).
2-Ethoxy-4-methyl-4-8N,N-dimethylamino)-thiazol-2-ine 89). A solution
of trimethylsulphonium iodide B3.04 g, 14 mmol) in dry DMSO B30 mL) was
added to sodium hydride B60% mineral oil dispersion) under argon B0.56 g,
14 mmol). The mixture was allowed to stir for 30 min. at room temperature,
then 8 B2.44 g, 14 mmol) in solution in dry DMSO B8mL) was added. The
mixture was stirred for 1 h at room temperature and added to water
B100 mL). The aqueous layer was extracted with diethyl ether B2*100 mL).
The organic layer was dried over magnesium sulfate, ®ltered and con-
centrated. The crude product was puri®ed by ¯ash chromatography on silica
gel eluting with petroleum ether=ethyl acetate B7=3) to get 9 as an oil in 40%
1
yield. H NMR BCDCl3; 200 MHz) d: 1.25 Bt, 3H, CH3-CH2, J ˆ 7.20); 1.38
Bs, 3H, CH3); 2.25 Bs, 6H, NBCH3)2); 3.04 Bd, 1H, H5a, J5a±5b ˆ 11.29); 3.44
Bd, 1H, H5b, J5b±5a ˆ 11.29); 4.24 Bq, 2H, CH2-CH3, J ˆ 7.20). 13C NMR
BCDCl3; 50 MHz) d: 14.4 BCH3-CH2); 26.1 BCH3); 39.0 BNBCH3)2); 41.3 BC-
5); 66.9 BCH2O); 93.7 BC-4); 163.8BC-2).
2-Ethoxy-4-methyl-thiazole 810). A mixture of thiazoline 12 B0.29 g,
1.3 mmol) in toluene B5 mL) was heated for 2h at re¯ux. After removal of the
solvent in vacuo, the crude product was puri®ed by ¯ash column chromato-
graphy on silica gel, eluting with petroleum ether=ethyl acetate B8=2), to get 10.
1H NMR BCDCl3; 200 MHz) d: 1.40 Bt, 3H, CH3CH2, J ˆ 7); 2.25 Bd, 3H,
CH3, JCH3-CH ˆ 1.22); 4.41 Bq, 2H, CH2, J ˆ 7); 6.18Bq, 1H, H5, J
ˆ
CH3±CH
1.22). 13C NMR BCDCl3; 50 MHz) d: 14.2 BCH3); 17.6 BCH3-C4); 62.7 BCH2);
‡
104.4 BC-5); 146.5 BC-4); 173.8BC-2). MS BEI) M =z B%): M ˆ 143; 115 B100);
87 B35); 71 B35); 70 B46); 46 B60); 45 B49); 42 B83); 29 B30); 27 B25). I.R. KBr
Bm cmÀ1) 2983; 1517; 1476; 1378; 1307; 1232; 1137; 1024.
4-Methyl-2H-1,3-thiazolin-2-oneꢀ11). To a solution of thiazole 10 B1 g,
3.41 mmol) in toluene B10 mL) was added phosphorus tribromide B0.2 mL,
2.38mmol). The mixture was heated at re¯ux for 2 h and 2 mL of water was
added. The mixture was cooled to room temperature and the aqueous layer
was extracted with dichloromethane B100 mL). The organic layer was dried
over magnesium sulfate, ®ltered and then concentrated. The crude product

THIAAZAHETEROCYCLE NUCLEOSIDE ANALOGUES
345
was puri®ed by ¯ash chromatography on silica gel, eluting with petroleum
1
ether=ethyl acetate B5=5), yielded 11 in 80% yield. m.p. 73±74ꢀC. H NMR
BCDCl3; 200 MHz) d: 2.11 Bd, 3H, CH3, JCH3±CH ˆ 1.22); 5.68Bq, 1H, H5,
JCH3±CH ˆ 1.22); 10.33 BNH). 13C NMR BCDCl3; 50 MHz) d: 14.4 BCH3);
‡
97.5 BC-5); 130.8BC-4); 176.4 BC-2). MS BEI) M =z B%): M ˆ 115; 91 B15); 87
B15); 71 B19); 46 B23); 45 B34); 42 B85). I.R. KBr Bm cmÀ1) 3090; 1646; 1445;
1219. Anal. Calcd for C4H5NOS: C, 41.72; H, 4.38; N, 12.16; S, 27.84.
Found: C, 41.43; H, 4.47; N, 11.61; S, 27.80.
2-Ethoxy-4-hydroxy-4-methyl-thiazol-2-ine 812). To a solution of
thiocarbamate 7 B1 g, 0.094 mol) in dry dichloromethane B10 mL) were
added triethylamine B2.7 mL, 0.19 mol) and chloroacetone B1.5 mL,
0.19 mol). The mixture was heated at 30ꢀC for 24 h and diluted with water
B100 mL). The aqueous layer was extracted with dichloromethane
B2*100 mL). The organic layer was dried over magnesium sulfate, ®ltered and
concentrated. The crude product was puri®ed by ¯ash chromatography on
silica gel, eluting with petroleum ether=ethyl acetate B5=5), to get 12 in 75%
1
yield. m.p. 86-88ꢀC. H NMR BCDCl3; 200 MHz) d: 1.34 Bt, 3H, J ˆ 7.20,
CH3CH2); 1.61 Bs, 3H, C4-CH3); 3.35 Bd, 1H, H5a, J5a±5b ˆ 11.20); 3.48Bd,
1H, H5b, J5a±5b ˆ 11.20); 4.29 Bq, 2H, J ˆ 7.20); 5.48B1H, OH). 13C NMR
BCDCl3; 50 MHz) d: 14.3 BCH3CH2); 29 BCH3); 45.7 BC-5); 67.5 BCH2O);
‡
101.0 BC-4); 168.3 BC-2). MS BEI) M=z B%): M ˆ 161; 146 B43); 118B23); 86
B84); 43 B100); 29 B37). I.R. KBr Bm cmÀ1) 3179; 2979; 1621; 1259; 1235; 1132.
3-83,5-Di-O-p-chlorobenzoyl-2-deoxy-a,b-D-ribofuranosyl)-6-methoxy-
carbonyl-4H-1,3-thiazin-2,4-dione 814). To a solution thiazindione 3 B0.3 g,
1.6 mmol) in dry acetonitrile B10 mL) was added DBU B0.26 mL, 1.76 mmol).
The mixture was cooled at 0ꢀC and stirred for 15 min. before the addition of
ribosyl chloride 137 B0.75 g, 1.76 mmol). The mixture was allowed to stir for
3 h at 0ꢀC, and water B100 mL) was added. The solution was extracted with
dichloromethane B2*100 mL) and the organic layers were washed with brine
and dried over magnesium sulfate, ®ltered and concentrated in vacuo. The
crude product was puri®ed by ¯ash chromatography on silica gel, eluting
with petroleum ether=ethyl acetate B9=1), to get 14 in 60% yield Ba=b ratio
1=1). The anomer 14a was recrystallized from diethyl ether. a anomer:
20
[a]D ˆ ‡21.9; BC ˆ 1.00, CHCl3). 1H NMR BCDCl3; 400 MHz) d: 2.79±2.84
Bm, 1H, H20a); 2.97±3.03 Bm, 1H, H20b); 3.87 Bs, 3H, OCH3); 4.46 Bdd, 1H,
H50a, J5 a±4 ˆ 3.60 and J5 a±5 b ˆ 11.90); 4.63 Bdd, 1H, H50b, J5 b±4 ˆ 4.80 and
0
0
0
0
0
0
J5 a±5 b ˆ 11.90); 4.89±4.92 Bm, 1H, H40); 5.44±5.55 Bm, 1H, H30); 6.23 Bdd, 1H,
H10, J ˆ 6.30 and 7.80); 7.03 Bs, 1H, H5); 7.41, 7.43 B2d, 4H, J ˆ 8.80, HAr);
7.92, 8.01 B2d, 4H, J ˆ 8.80, HAr). 13C NMR BCDCl3; 100 MHz) d: 34.5 BC-
20); 52.9 BOCH3); 64.1 BC-50); 73.9 BC-30); 82.3 BC-40); 82.7 BC-10); 119.4 BC-5);
127.6 to 140.0 BC-Ar); 140.0 BC-4); 164.1, 168.5 BC-2, C-4); 164.9, 165.6 BCˆO
0
0
20
ester); 165.2 BCˆO ester). b anomer: [a]D ˆ À21.8BC ˆ 1.00, CHCl3). m.p.

346
ANE ET AL.
1
157±159ꢀC. H NMR BCDCl3; 400 MHz) d: 2.43±2.50 Bm, 1H, H20a); 3.21±
3.29 Bm, 1H, H20b); 3.87 Bs, 3H, OCH3); 4.45±4.49 Bm, 1H, H40); 4.57 Bdd, 1H,
H50a, J ˆ 6 and 11.77); 4.66 Bdd, 1H, H50b, J ˆ 5 and 11.77); 5.76±5.8Bm, 1H,
H30); 6.30 Bdd, 1H, H10, J ˆ 6.34 and 7.39); 7.01 Bs, 1H, H5); 7.38, 7.42 B2d,
4H, HAr, J ˆ 8.55); 7.94, 7.99 B2d, 4H, HAr, J ˆ 8.55). 13C NMR BCDCl3;
100 MHz) d: 39.9 BC-20); 52.9 BOCH3); 64.1 BC-50); 74.9 BC-30); 82.3 BC-40);
82.4 BC-10); 119.6 BC-5); 127.7 to 140.1 BC-Ar); 140.1 BC-4); 163.9, 168.3 BC-2,
‡
‡
C-4); 164.9, 165.4 BCˆO ester); 165.6 BCˆO ester). MS {BCI , NH4 ),
‡
M 18 ˆ 597}; BEI) M=z B%): 267 B20); 141 B20); 139 B60); 81 B100). I.R.
KBr Bm cmÀ1) 1721; 1696; 1327; 1277; 1093; 1015; 761. Anal. Calcd for
C25H19Cl2NO9S: C, 51.74; H, 3.30; Cl, 12.22; N, 2.41; S, 5.52. Found: C,
‡
51.84; H, 3.42; Cl, 12.35; N, 2.32; S, 5.21. BLSIMS with Cs , Positif in
‡
‡
Micromasse)±BCalcd.: [M‡ H] : 580.02367. Found: [M‡ H] : 580.0226
5-Acetyl-3-83,5-di-O-p-chlorobenzoyl-2-deoxy-a,b-D-ribofuranosyl)-3,6-di-
hydro-2H-1,3-thiazin-2-one 815). The protected nucleoside 15 was obtained
by following a similar procedure as in the preparation of 14, from thiazinone
6 B0.5 g, 3.18mmol) and ribosyl chloride 137 B1.5 g, 3.5 mmol). The crude
product was puri®ed by ¯ash chromatography on silica gel, eluting with
petroleum ether=ethyl acetate B8=2), to get 15 in 75% yield Ba=b ratio 2=1).
20
a anomer : [a]D ˆ ‡43.2 BC ˆ 1.00, CHCl3), 1H NMR BCDCl3; 200 MHz) d:
2.18Bs, 3H, CH ); 2.43±2.53 Bm, 1H, H20a); 2.86±3.00 Bm, 1H, H20b); 3.63,
3
3.70 Bdd, 1H, H4a, J4a±6 ˆ 1.10 and J4a±4b ˆ 15.10); 3.90 Bd, 1H, H4b,
J4a±4b ˆ 15.10); 4.53±4.57 Bm, 2H, H50a, H50b); 4.79±4.84 Bm, 1H, H40, J4 ±5
ˆ
0
0
0
0
0
0
4.5 and J4 ±3 ˆ 1.37); 5.53±5.58Bm, 1H, H3 ); 6.33 Bdd, 1H, H1 , J ˆ 2.28et
6.70); 7.39 et 7.45 B2d, 4H, HAr, J ˆ 8.70); 7.61 Bd, 1H, H6, J6±4a ˆ 1.10);
7.86±7.99 B2d, 4H, HAr, J ˆ 8.7). 13C NMR BCDCl3; 50 MHz) d: 23.6 BC-4);
24.7 BCH3); 39.1 BC-20); 64.1 BC-50); 75.0 BC-30); 84.5 BC-40); 88.0 BC-10); 113.9
BC-5); 127.2 to 140.5 BC-Ar); 140.6 BC-6); 164.9, 165.1 BCˆO ester); 167.3
BC-2); 193.7 BCˆO). I.R. KBr Bm cmÀ1) 1723, 1636, 1269, 1233, 1092, 1015,
20
759. b anomer: [a]D ˆ À11.1 BC ˆ 1.00, CHCl3), 1H NMR BCDCl3;
200 MHz) d: 2.11 Bs, 3H, CH3); 2.24±2.39 Bm, 1H, H20a); 2.67±2.78Bdd, 1H,
H20b, J2 b±1 ˆ 5.37 and J2 b±2 a ˆ 14.2); 3.62 Bdd, 1H, H4a, J4a±6 ˆ 0.91 and
0
0
0
0
J4a±4b ˆ 15.3); 3.82 Bd, 1H, H4b, J4b±4a ˆ 15.3); 4.51±4.56 Bm, 1H, H40);
4.65 Bdd, 1H, H50a, J5 a±4 ˆ 4.47 and J5 a±5 b ˆ 12.11); 4.76 Bdd, 1H, H50b,
0
0
0
0
J5 b±4 ˆ 3.1 and J5 a±5 b ˆ 12.11); 5.58±5.61 Bm, 1H, H30); 6.42 Bdd, 1H, H10,
J ˆ 5.37 and 8.70); 7.41, 7.45 B2d, 4H, HAr, J ˆ 2.90); 7.50 Bd, 1H, H6,
J4a±6 ˆ 0.91); 7.94, 7.99 B2d, 4H, HAr, J ˆ 8.55). 13C NMR BCDCl3; 50 MHz)
d: 23.3 BC-4; 24.5 BCH3); 37.9 BC-20); 64.5 BC-50); 74.9 BC-30); 82.4 BC-40); 85.5;
BC-10); 115.3 BC-5); 127.4 to 140.3 BC-Ar); 140.3 BC-6); 165.1, 165.2 BCˆO
0
0
0
0
‡
‡
‡
ester); 167.7 BC-2); 193.8BC ˆO). MS {BCI , NH4 ), M 18 ˆ 567}; BEI) M=z
B%): 156 B30); 141 B29); 139 B86); 110 B35); 81 B100); 75 B21); 44 B23); 28 B23).
I.R. KBr Bm cmÀ1) 1725; 1639; 1593; 1403; 1311; 1092; 759. Anal. Calcd for
C25H21Cl2NO7S: C, 54.55; H, 3.85; Cl, 12.88; N, 2.54; S, 5.82. Found: C,

THIAAZAHETEROCYCLE NUCLEOSIDE ANALOGUES
347
‡
54.33; H, 3.90; Cl, 13.26; N, 2.52; S, 4.98. BLSIMS with Cs , Positif in
‡
‡
Micromasse) BCalcd. : [M ‡ H] : 550.04947. Found: [M ‡ H] : 550.0488
3-83,5-Di-O-p-chlorobenzoyl-2-deoxy-a,b-D-ribofuranosyl)-4-methyl-2H-
1,3-thiazolin-2-one 816). The protected nucleoside 15 was obtained by fol-
lowing a similar procedure as in the preparation of 14 from thiazolinone 11
B0.21 g, 1.83 mmol) and ribosyl chloride 137 B0.87 g, 2.01 mmol). The crude
product was puri®ed by column chromatography on silica gel eluting with
petroleum ether=ethyl acetate 9=1 to get 16 in 20% yield Ba=b ratio 9=1). a
20
1
anomer: [a]D ˆ ‡66.1 BC ˆ 1.00, CHCl3). H NMR BCDCl3; 400 MHz) d:
0
2.21 Bs, 3H, CH3); 2.92±2.98Bm, 1H, H2 a); 3.06±3.13 Bm, 1H, H20b); 4.50
Bdd, 1H, H50a, J5 a±4 ˆ 5.1 and J5 a±5 b ˆ 12.04); 4.7 Bdd, 1H, H50b,
0
0
0
0
J5 b±4 ˆ 4.74 and J 5 b±5 a ˆ 12.04); 4.87±4.91 Bm, 1H, H40); 5.46±5.51 Bm, 1H,
0
0
0
0
H30); 5.73±5.76 Bm, 1H, H4); 5.93 Bt, 1H, H10, J1 -2 ˆ 7.22); 7.37, 7.42 Bd, 4H,
HAr, J ˆ 8.1); 7.94, 7.98 Bd, 4H, HAr, J ˆ 8.1). 13C NMR BCDCl3; 100 MHz)
d: 16.1 BCH3); 34.7 BC-20), 63.4 BC-50), 74.3 BC-30), 80.9 BC-40), 84.6 BC-10), 97.3
BC-4), 127.9 to 140.1 BC-Ar), 132.1 BC-5); 161.41, 161.43 BCˆO ester),
0
0
20
173.2 BC-2). b anomer: [a]D ˆ À6.3 BC ˆ 1.00, CHCl3).1H NMR BCDCl3;
400 MHz) d: 2.21 Bs, 3H, CH3); 2.24±2.47 Bm, 1H, H20a); 3.34±3.41 Bm, 1H,
H20b); 4.42 Bm, 1H, H40); 4.62 Bdd, 1H, H50a, J5 a±4 ˆ 5.8and J 5 a±5 b ˆ 11.8);
0
0
0
0
4.70 Bdd, 1H, H50b, J5 b±4 ˆ 4.7 and J5 a±5 b ˆ 11.8); 5.72±5.76 Bm, 2H, H30,
0
0
0
0
H4); 5.99 Bt, 1H, H10, J1 ±2 a ˆ 7.05); 7.40, 7.43 B2d, 4H, HAr, J ˆ 8.55); 7.96,
7.99 B2d, 4H, HAr, J ˆ 8.55). 13C NMR BCDCl3; 100 MHz) d: 16.0 BCH3);
34.6 BC-20); 64.4 BC-50); 75.5 BC-30); 81.7 BC-40); 84.4 BC-10); 98.8 BC-4); 127.8
to 139.9 BC-Ar); 132.0 BC-5); 164.9, 165.4 BCˆO ester); 172.7 BC-2). MS
0
0
‡
‡
{BCI , NH4 ), M‡18 ˆ 526}; BEI) M=z B%): 236 B33), 141 B43), 139 B97), 111
B30), 81 B100). Anal. Calcd for C23H19Cl2NO9S: C, 54.34; H, 3.77; Cl, 13.95;
N, 2.76; S, 6.31. Found: C, 53.87; H, 3.81; Cl, 15.74; N, 2.41; S, 3.64.
1-8Methoxycarbonylacetylene)amide-N-82-deoxy-a,b-D-ribofuranosyl) 817).
A solution of 14b B0.2 g, 0.34 mmol) in dry methanol B10 mL) was treated with
sodium methoxide in methanol B0.76 mL, 0.76 mmol). The mixture was stirred
for 2 h at 0ꢀC, diluted with water B10 mL) and extracted with dichloromethane
B2*30 mL). The organic layer was washed with brine B2*50 mL), dried over
magnesium sulfate, ®ltered and concentrated in vacuo. The crude product was
puri®ed by ¯ash chromatography on silica gel, eluting with methanol=ethyl
acetate B1=9), to give an anomeric mixture of 17 as a colorless oil in 95% yield.
1H NMR BCDCl3; 200 MHz) d: 2.80, 2.90, 2.95, 2.37 B4m, 4H, 2*H2a, 2*H2b);
3.44 Bm, 4H, 2*H5a, 2*H5b); 3.66 Bs, 6H, 2*CO2CH3); 3.70 Bm, 2H, 2*H4); 4.12
Bm, 2H, 2*H3); 5.58Bm, 2H, 2*H1); 7.58, 7.75 B2d, 2H, 2*NH). 13C NMR
BCDCl3; 50 MHz) d: 3.5 BC-2); 51.2 BCO2CH3); 61.4, 62.2 BC-5); 70.3, 70.7
BC-3); 81.0, 81.8 BCꢁC); 84.6 BC-1); 86.1 BC-4); 97.2 BC-5); 132.3 BC-4); 174.1 BC-
2); 155.7, 155.9, 181.4 BCˆO). MS BEI) M=z B%) : 160 B81); 142 B35); 131 B30);
130 B25); 117 B63); 116 B44); 114 B24); 110 B20); 104 B56); 102 B96); 99 B25); 88

348
ANE ET AL.
B43); 85 B81); 76 B82); 59 B100)±MS BCI) BNH3): 209. I.R. KBr Bm cmÀ1): 3426;
2922; 2852; 1700; 1636; 1565; 1420; 1123.
1-Methoxycarbamate-N-82-deoxy-a,b-D-ribofuranosyl) 818). A solution
of 15b B0.5 g, 0.86 mmol) in dry methanol B10 mL) was treated with sodium
methoxide in methanol B0.086 mL, 0.086 mmol) at room temperature until
the consumption of starting material Bmonitored by TLC). After removal of
the solvent in vacuo, the crude product was puri®ed by ¯ash chromatography
on silica gel, eluting with petroleum ether=ethyl acetate B7=3) then ethyl
1
acetate=methanol B95=5), to get a mixture of anomers 18 in 60% yield. H
NMR BDMSO-d6; 200 MHz) 1.75±1.87 Bm, 1H, H2a for DIA I); 1.91±1.98
Bm, 2H, H20a, H20b for DIA II); 2.27±2.40 Bm, 1H, H2b for DIA I); 3.39±3.47
Bm, 4H, H5a, H5b, H50a, H50b); 3.62 Bs, 6H, 2BOCH3); 3.66±3.79 Bm, 2H, H4,
0
H40); 3.98±4.18 Bm, 2H, H3, H30); 5.40±5.58Bm, 2H, H1, H1 ); 7.59, 7.75
2*Bd, 1H, NH, J1 ˆ 8.84 and J2 ˆ 9). 13C NMR BDMSO-d6; 50MHz) 40.2,
40.6 BC-2); 51.2 BOCH3); 61.4, 62.3 BC-5); 70.3, 70.5 BC-3); 81.0, 81.8 BC-4);
‡
84.7, 86.1 BC-1); 155.7, 156.0 BCˆO). MS; EI, M=z B%): {CI, NH4 :
M‡18 ˆ 209} 160 B81); 142 B35); 131 B30); 130 B25); 117 B63); 116 B44); 114
B24); 110 B20); 104 B56); 103 B28); 102 B96); 99 B25); 98 B26); 88 B43); 85 B81); 76
B82); 73 B27); 72 B40); 70 B40); 60 B19); 59 B100); 58 B54); 57 B32); 56 B42); 45
B63); 44 B83); 43 B63); 33 B39); 31 B69); 30 B48); 29 B30).
3-82-Deoxy-b-ribofuranosyl)-4-methyl-2H-1,3-thiazolin-2-one 819b).
Compound 16b B0.35 g, 0.7 mmol) dissolved in THF:H2O mixture Bv=v:7:3)
B10 mL) was treated with 1M KOH B1.5 mL, 1.5 mmol). The mixture was
stirred at room temperature for 3 h the solvent was removed in vacuo and the
crude product was puri®ed by ¯ash chromatography on silica gel, eluting
20
with ethyl acetate, to get 19b in 80% yield. [a]D ˆ ‡2.00 BC ˆ 1.00, CHCl3).
1H NMR BCDCl3; 400 MHz) d: 2.08±2.13 Bm, 1H, H20a,); 2.17 Bs, 3H, CH3);
3.02±3.09 Bm, 1H, H20b); 3.73 Bdd, 1H, H50a, J5 a±4 ˆ 2.80 and J5 a±5 b
ˆ
0
0
0
12.26); 3.86 Bdd, 1H, H50b, J5 b±4 ˆ 2.39 and J5 b±5 a ˆ 12.26); 3.98±4.01
0
0
0
0
Bm, 1H, H40); 4.64±4.66 Bm, 1H, H30); 5.79 Bs, 1H, H4); 5.85 Bt, 1H, H10,
13
J1 -2 ˆ 7.42). C NMR BCDCl3; 100 MHz) d: 16.0 BCH3); 37.3 BC-20); 63.0
0
0
BC-50); 72.3 BC-30); 85.8 BC-40); 87.9 BC-10); 97.3 BC-4); 132.6 BC-5); 174.3
‡
BC-2). BLSIMS with Cs , Positif in Micromasse) -Calcd for C9H13NO4S:
‡
‡
[M ‡ H] ˆ 231.0565. Found: [M ‡ H] ˆ 231.0536.
Methyl 3-O-tert-Butyldiphenylsilyl-2-deoxy-5-O-thiocarbamoyl-a,b-D-
ribofuranoside 821). Sodium hydride B60% mineral oil dispersion) B60 mg,
1.5 mmol) was added to freshly distilled tetrahydrofuran B10 mL). The
solution was cooled at 0ꢀC and 20 B450 mg, 1.16 mmol), in dry tetra-
hydrofuran B2 mL), was added dropwise under argon. After 15 min, carbon
disulfure B0.09 mL, 1.5 mmol) was added to the mixture followed by iodo-
methane B0.09 mL, 1.5 mmol) after 30 min. The mixture was allowed to stir

THIAAZAHETEROCYCLE NUCLEOSIDE ANALOGUES
349
at room temperature for 1h and the mixture was concentrated in vacuo,
extracted with dichloromethane B20 mL). The organic layer was washed with
brine B2*20 mL), dried over magnesium sulfate, ®ltered and concentrated in
vacuo. The crude product was puri®ed by ¯ash chromatography on silica gel,
eluting with petroleum ether, to get 3-O-tert-butyldiphenylsilyl-2-deoxy-1-O-
methyl-5-O-Bmethylthio)carbonyl-a,b-D-ribofuranoside in 95% as a yellow
foamy solid. Ammonia gas was bubbled for 1 h in a solution of the 50-car-
bamate ribofuranose B300 mg, 0.629 mmol) dissolved in ethanol B20 mL).
Then the mixture was stirred for 12 h at room temperature and the solution
was degassed, ®ltered on celite, concentrated in vacuo. The crude product
was puri®ed by ¯ash chromatography on silica gel, eluting with petroleum
ether=ethyl acetate B8=2), to give 21 in 95% as a yellow foamy solid. anomer1:
1H NMR BCDCl3; 400 MHz) d: 1.06 Bs, 9H, CBCH3)3); 1.99 Bddd, 1H, H2a,
J2a±2b ˆ 13.2, J2a±1 ˆ 1.8and J
ˆ 6.8); 2.11 Bdt, 1H, H2b, J2a±2b ˆ 13.2,
2a±3
J2b±1 ˆ 5.4 and J2b±3 ˆ 5.4); 3.25 Bs, 3H, OCH3); 4.11 Bdd, 1H, H5a,
J5a±5b ˆ 11.0 and J5a±4 ˆ 6.5); 4.22 Bm, 1H, H4); 4.32 Bdd, 1H, H5b,
J5a±5b ˆ 11.0 and J5b±4 ˆ 4.7); 4.38Bm, 1H, H3); 5.05 Bdd, 1H, H1, J
ˆ 1.8
2a±1
and J2b±1 ˆ 5.4); 5.80 Bs, 1H, NH); 6.30 Bs, 1H, NH); 7.40 Bm, 6H, HAr); 7.65
Bm, 4H, HAr). 13C NMR BCDCl3; 100 MHz) d: 19.0 BCBCH3)3); 26.9
BCBCH3)3); 41.9 BC-2); 54.9 BOCH3); 71.7 BC-5); 73.6 BC-3); 83.8 BC-4); 105.4
1
BC-1); 127.8to 135.7 BC-Ar); 192.1 BC ˆS). anomer 2: H NMR BCDCl3;
400 MHz) d: 1.06 Bs, 9H, CBCH3)3); 1.89 Bddd, 1H, H2a, J2a±2b ˆ 13.8,
J2a±1 ˆ 2.6 and J2a±3 ˆ 4.9); 2.10 Bddd, 1H, H2b, J2a±2b ˆ 13.8, J2b±1 ˆ 5.8and
J2b±3 ˆ 8.1); 3.38 Bs, 3H, OCH3); 4.12 Bdd, 1H, H5a, J5a±5b ˆ 10.2 and
J5a±4 ˆ 7.5); 4.12 Bm, 2H, H5b, H3, J5a±5b ˆ 11.4 and J5b±4 ˆ 4.7); 4.21 Bm, 1H,
H4); 4.44 Bdd, 1H, H5b, J5a±5b ˆ 11.4 and J5b±4 ˆ 3.1); 4.90 Bdd, 1H, H1,
J2a±1 ˆ 2.6 and J2b±1ˆ5.8); 5.90 Bs, 1H, NH); 6.40 Bs, 1H, NH); 7.40 Bm, 6H,
HAr); 7.68Bm, 4H, HAr). 13C NMR BCDCl3; 100 MHz) d: 19.1 BCBCH3)3);
26.9 BCBCH3)3); 41.5 BC-2); 55.1 BOCH3); 70.3 BC-5); 72.7 BC-3); 81.4 BC-4);
104.6 BC-1); 127.8to 135.8BC-Ar); 192.1 BC ˆS).
Methyl 3-O-tert-Butyldiphenylsilyl-2-deoxy-5-O-[84-dimethylamino)-
1-thia-3-aza-1,3-butadienyl]-a,b-D-ribofuranoside 822a). To a solution of 21
B0.3 g, 0.67 mmol) in dry dichloromethane B10 mL) was added N,N-dimethyl-
formamide dimethyl acetal B0.1 mL, 0.74 mmol) dropwise. The solution was
stirred at room temperature for 1 h and concentrated in vacuo. The crude
product was puri®ed by ¯ash chromatography on silica gel, eluting with
petroleum ether=ethyl acetate B4=6), to get 22a in 95% as a yellow syrup. MS
BEI) M=z B%): 213 B32); 199 B58); 183 B27); 116 B29); 99 B100); 81 B61). MS BCI)
‡
BNH3) [M‡H ] ˆ 501ÀI.R. KBr Bm cmÀ1): 3071; 3047; 2932; 2857; 1630;
1
1280; 1229; 1114; 706; 506. anomer 1: H NMR BCDCl3; 400 MHz) d: 1.05
Bs, 9H, CBCH3)3); 1.98Bddd, 1H, H2a, J
J2a±3 ˆ 6.05); 2.05 Bdt, 1H, H2b, J2a±2b ˆ 13.0, J2b±1 ˆ 5.2 and J2b±3 ˆ 5.2); 3.11
ˆ 13.0, J2a±1 ˆ 2.05 and
2a±2b

350
ANE ET AL.
Bs, 3H, NCH3); 3.19 Bs, 3H, NCH3); 3.26 Bs, 3H, OCH3); 4.34, 4.42 B2*m,
2*2H, H3, H4, H5a, H5b); 5.05 Bdd, 1H, H1, J2a±1 ˆ 2.05 and J2b±1 ˆ 5.2);
13
0
7.38Bm, 6H, HAr); 7.65 Bm, 4H, HAr); 8.73 Bs, 1H, H4 )± C NMR BCDCl3;
100 MHz) d: 19.1 BCBCH3)3); 26.9 BCBCH3)3); 36.3 BNCH3); 41.9 BNCH3);
42.1 BC-2); 55.0 BOCH3); 72.5 BC-5); 74.2 BC-3); 84.1 BC-4); 105.5 BC-1); 127.8
1
to 135.9 BC-Ar); 164.0 BC-40); 205.0 BCˆS). anomer 2: H NMR BCDCl3;
400 MHz) d 1.87 Bddd, 1H, H2a, J2a±2b ˆ 13.7, J2a±1 ˆ 2.3 and J2a±3 ˆ 4.5);
2.10 Bddd, 1H, H2b, J2a±2b ˆ 13.7, J2b±1 ˆ 5.7 and J2b±3 ˆ 8.0); 3.09 Bs, 3H,
NCH3); 3.19 Bs, 3H, NCH3); 3.38Bs, 3H, OCH 3); 4.21 Bm, 1H, H3); 4.22 Bdd,
1H, H5a, J5a±5b ˆ 11.8and J 5a±4 ˆ 6.3); 4.34 Bm, 2H, H4); 4.45 Bdd, 1H, H5b,
J5a±5b ˆ 11.8and J
ˆ 2.7); 4.93 Bdd, 1H, H1, J2a±1 ˆ 2.35 and J2b±1 ˆ 5.7);
5b±4
7.35 Bm, 6H, HAr); 7.64 Bm, 4H, HAr); 8.72 Bs, 1H, H40). 13C NMR BCDCl3;
100 MHz) d: 19.2 BCBCH3)3); 27.0 BCBCH3)3); 36.3 BNCH3); 41.6 BC-2); 41.9
BNCH3); 55.1 BOCH3); 70.9 BC-5); 73.3 BC-3); 81.9 BC-4); 104.8 BC-1); 127.7 to
135.9 BC-Ar); 163.9 BC-40); 205.1 BCˆS).
Methyl 3-O-tert-Butyldiphenylsilyl-2-deoxy-5-O-[84-dimethylamino)-1-
thia-3-aza-1,3-pentadienyl]-a,b-D-ribofuranoside 822b). To a solution of 21
B0.35 g, 0.78mmol) in dry dichloromethane B10 mL) was added N, N-dimethyl-
acetamide dimethyl acetal B0.23 mL, 1.56 mmol) dropwise. The solution was
stirred at re¯ux for 5 h, cooled, and concentrated in vacuo. The crude pro-
duct was puri®ed by ¯ash chromatography on silica gel, eluting with petro-
leum ether=ethyl acetate B4=6), to get 22b in 95% as a yellow syrup. MS BEI)
M=z B%): 514; 311 B28); 254 B22); 213 B27); 199 B51); 197 B26); 183 B40); 181
B37); 163 B32); 135 B51); 129 B39); 113 B100); 91 B28); 87 B26); 81 B22); 72 B23);
71 B26) À I.R. KBr Bm cmÀ1): 3071; 2956; 2932; 2344; 1588; 1370; 1109; 1048;
706; 506. -Anal. Calcd for C27H38N2O4SSi : C, 63.00; H, 7.44; N, 5.44.
Found: C, 62.79; H, 7.51; N, 5.44. anomer1: 1H NMR BCDCl3; 400 MHz) d:
1.06 Bs, 9H, CBCH3)3); 1.93 Bddd, 1H, H2a, J2a±2b ˆ 13.3, J2a±1 ˆ 2.2 and
J2a±3 ˆ 6.6); 2.04 Bdt, 1H, H2b, J2a±2b ˆ 13.3 and J2b±1 ˆ 5.4); 2.32 Bs, 3H, C-4-
CH3); 3.06 Bs, 3H, NCH3); 3.08Bs, 3H, NCH 3); 3.26 Bs, 3H, OCH3); 4.13 Bdd,
1H, H5a, J5a±5b ˆ 11.4 and J5a±4 ˆ 7.5); 4.28Bdd, 1H, H5b, J
ˆ 11.4 and
5a±5b
J5b±4 ˆ 4.5); 4.35 Bm, 1H, H4); 4.43 Bm, 1H, H3); 5.05 Bdd, 1H, H1, J2a±1 ˆ 2.2
and J2b±1 ˆ 5.2); 7.38Bm, 6H, HAr); 7.66 Bm, 4H, HAr). 13C NMR BCDCl3;
100 MHz) d: 17.7 BC-50); 19.1 BCBCH3)); 27.0 BCBCH3)); 38.7 BNCH3); 38.9
BNCH3); 42.1 BC-2); 55.0 BOCH3); 72.2 BC-5); 74.2 BC-3); 84.4 BC-4); 105.5
1
0
BC-1); 127.8to 135.9 BC-Ar); 165.1 BC-4 ); 196.7 BCˆS). anomer 2: H NMR
BCDCl3; 400 MHz) d: 1.06 Bs, 9H, CBCH3)3); 1.85 Bm, 1H, H2a); 2.07 Bm, 1H,
H2b); 2.34 Bs, 3H, C-4-CH3); 3.06 Bs, 3H, NCH3); 3.08Bs, 3H, NCH ); 3.37
3
Bs, 3H, OCH3); 4.11 Bdd, 1H, H5a, J5a±5b ˆ 11.7 and J5a±4 ˆ 5.7); 4.22 Bm, 1H,
H3); 4.27 Bm, 1H, H4); 4.38Bdd, 1H, H5b, J 5a±5b ˆ 11.7 and J5b±4 ˆ 2.5); 4.92
Bm, 1H, H1); 7.39 Bm, 6H, HAr); 7.65 Bm, 4H, HAr); 8.72 Bs, 1H, H40). 13C
NMR BCDCl3; 100 MHz) d: 17.7 BC-50); 19.1 BCBCH3)3); 27.0 BCBCH3)3); 38.7

THIAAZAHETEROCYCLE NUCLEOSIDE ANALOGUES
351
BNCH3); 38.9 BNCH3); 41.6 BC-2); 55.1 BOCH3); 70.4 BC-5); 73.1 BC-3); 82.1
0
BC-4); 104.8BC-1); 127.7 to 135.8BC-Ar); 165.1 BC-4 ); 196.7 BCˆS).
Methyl 3-O-tert-Butyldiphenylsilyl-2-deoxy-5-O-[2-86-methoxycarbonyl)-
4-oxo-4H-1,3-thiazine-4-onyl]-a,b-D-ribofuranoside 823). To a solution of
21 B0.2 g, 0.45 mmol) in methanol B2 mL) was added dimethyl acet-
ylenedicarboxylate B0.11 mL, 0.90 mmol) dropwise. The mixture was stirred
at room temperature for 24 h and diluted with dichloromethane B20 mL).
The organic layer was washed with brine B3*50 mL), dried over magnesium
sulfate, ®ltered and concentrated in vacuo. The crude product was puri®ed by
¯ash chromatography on silica gel, eluting with petroleum ether=ethyl acet-
ate B9=1), to give 23 in 70% as a white foamy solid. MS BEI) M=z B%) :
498 B47); 268 B27); 213 B80); 199 B25); 183 B59); 135 B31); 81 B100) MS BCI)
‡
‡
BNH3) [M‡H ] ˆ 556 [M‡NH4 ] ˆ 578. anomer 1: 1H NMR BCDCl3;
400 MHz) d: 1.06 Bs, 9H, CBCH3)3); 2.07 Bddd, 1H, H2a, J2a±2b ˆ 13.1,
J2a±1 ˆ 1.4 and J2a±3 ˆ 6.8); 2.16 Bddd, 1H, H2b, J2a±2b ˆ 13.1, J2b±1 ˆ 5.2 and
J2b±3 ˆ 6.4); 3.22 Bs, 3H, OCH3); 3.86 Bs, 3H, CO2CH3); 4.26 Bm, 1H, H4);
4.28Bdd, 1H, H5a, J
ˆ 10.1 and J5b±4 ˆ 6.0); 4.36 Bdd, 1H, H5b,
5a±5b
J5a±5b ˆ 10.1 and J5b±4 ˆ 4.1); 4.45 Bm, 1H, H3); 5.05 Bdd, 1H, H1, J2a±1 ˆ 1.4
and J2b±1 ˆ 5.2); 7.02 Bs, 1H, H50); 7.40 Bm, 6H, HAr); 7.63 Bm, 4H, HAr). 13C
NMR BCDCl3; 100 MHz) d: 19.1 BCBCH3)); 27.0 BCBCH3)); 42.1 BC-2); 53.0
BCO2CH3); 55.0 BOCH3); 73.2 BC-3); 74.8BC-5); 83.3 BC-4); 105.5 BC-1); 120.2
BC-50); 128.0 to 135.8 BC-Ar); 146.6 BC-60); 166.3 BCO2CH3); 177.9 BC-40);
190.0 BC-20). anomer 2: 1H NMR BCDCl3; 400 MHz) d: 1.06 Bs, 9H,
CBCH3)3); 1.98Bddd, 1H, H2a, J 2a±2b ˆ 13.7, J2a±1 ˆ 2.6 and J2a±3 ˆ 4.6); 2.24
Bm, 1H, H2b); 3.39 Bs, 3H, OCH3); 3.87 Bs, 3H, CO2CH3); 4.21 Bm, 3H, H3,
H4, H5a); 4.54 Bdd, 1H, H5b, J5a±5b ˆ 11.3 and J5b±4 ˆ 1.5); 4.93 Bdd, 1H, H1,
J2a±1 ˆ 2.6 and J2b±1 ˆ 5.7); 7.02 Bs, 1H, H50); 7.40 Bm, 6H, HAr); 7.63 Bm, 4H,
HAr). 13C NMR BCDCl3; 100 MHz) d: 19.0 BCBCH3)3); 26.8BCB CH3)3); 41.5
BC-2); 52.7 BCO2CH3); 55.1 BOCH3); 72.0 BC-3); 72.9 BC-5); 80.6 BC-4); 104.5
0
BC-1); 119.5 BC-50); 127.8to 135.7 BC-Ar); 146.4 BC-6 ); 166.0 BCO2CH3);
177.5 BC-40); 189.8 BC-20).
Methyl 3-O-tert-Butyldiphenylsilyl-2-deoxy-5-O-[2-5-acetyl-6H-1,3-thia-
zin-2-yl]-a,b-ribofuranoside 824). A solution of 22a B0.1 g, 0.2 mmol) in
methyl vinyl ketone B2 mL) was heated at re¯ux for 2 h. The mixture was
diluted with dichloromethane B10 mL) and washed with brine B2*20 mL).
After extraction with dichloromethane, the organic layer was dried over
magnesium sulfate, ®ltered and concentrated in vacuo. The crude product
was puri®ed by ¯ash chromatography on silica gel, eluting with petroleum
ether=ethyl acetate B8=2), to get 24 in 80% as a white foamy solid. 1H NMR
BCDCl3; 400 MHz) d: 1.06 Bs, 9H, CBCH3)3); 1.91 Bddd, 1H, H2a,
J2a±2b ˆ 13.7, J2a±1 ˆ 2.5 and J2a±3 ˆ 7.4); 2.16 Bm, 1H, H2b); 2.37 Bs, 3H,
0
CO2CH3); 3.39 Bs, 3H, OCH3); 3.68Bs, 2H, H6 ); 4.08Bdd, 1H, H5a,

352
ANE ET AL.
J5a±5b ˆ 11.8and J
J5a±5b ˆ 11.8and J
ˆ 4.4); 4.20 Bm, 2H, H3, H4); 4.38Bdd, 1H, H5b,
ˆ 2.5); 4.93 Bdd, 1H, H1, J2a±1 ˆ 2.5 and J2b±1 ˆ 5.7);
5a±4
5b±4
7.38Bm, 6H, HAr); 7.55 Bs, 1H, H4 0); 7.63 Bm, 4H, HAr). 13C NMR BCDCl3;
100 MHz) d: 19.3 BCBCH3)3); 23.1 BC-60); 25.4 BCOCH3); 27.0 BCBCH3)3); 41.7
BC-2); 55.4 BOCH3); 68.0 BC-5); 72.6 BC-3); 81.4 BC-4); 104.8 BC-1); 115.7
BC-50); 127.9 to 136.0 BC-Ar); 147.9 BC-60); 167.7 BC-20); 195.9 BCOCH3). MS
BEI) M=z B%): 213 B24); 199 B100); 183 B23); 81 B33). MS BCI) BNH3)
‡
[M‡H ] ˆ 526. I.R. KBr Bm cmÀ1): 2931; 2856; 1698; 1111; 739; 502.
Methyl 3-O-tert-Butyldiphenylsilyl-2-deoxy-5-O-[2-84-methyl)-1,3-thiazol
-2-yl]-a,b-D-ribofuranoside 825). Sodium hydride B60% mineral oil disper-
sion) B96 mg, 2.41 mmol) was added to a solution of trimethyl sulfonium
iodide B530 mg, 2.41 mmol) in freshly distilled dimethylsulfoxide B15 mL).
After stirring at room temperature for 30 min 22b B620 mg, 1.2 mmol) was
added. Stirring was continued for 12 h. The mixture was diluted with ethyl
acetate B60 mL) and washed with water B3*60 mL). The organic layer was
dried over magnesium sulfate, ®ltered and concentrated in vacuo. The thia-
zoline intermediate obtained as a white foamy solid B700 mg, 1.32 mmol) was
dissolved in dry toluene B20 mL) and treated with iodomethane B0.25 mL,
3.96 mmol). The mixture was stirred under argon at re¯ux for 2 h. The
solution was ®ltered on celite, concentrated under vacuo. Dichloromethane
B30 mL) was added and the solution was washed with brine B2*30 mL). After
extraction, the organic layer was dried over magnesium sulfate, ®ltered and
concentrated in vacuo. The crude product was puri®ed by ¯ash chromato-
graphy on silica gel, eluting with petroleum ether=ethyl acetate B9=1), to get
‡
25 in 50% as a colorless syrup. MS BCI) BNH3) [M‡H ] ˆ 484. I.R. KBr
1
Bm cmÀ1) : 3071; 3049; 2952; 2857; 1517; 1305; 112; 703. anomer 1: H NMR
BCDCl3, 400 MHz) d: 1.06 Bs, 9H, CBCH3)3); 1.91 Bddd, 1H, H2a,
J2a±2b ˆ 13.5 , J2a±1 ˆ 2.4 , J2a±3 ˆ 4.4); 2.15 Bddd, 1H, H2b, J2a±2b ˆ 13.5,
J2b±1 ˆ 5.7 , J2b±3 ˆ 7.7); 2.23 Bs, 3H, C-40-CH3); 3.39 Bs, 3H, OCH3); 4.11 Bdd,
1H, H5a, J5a±5b ˆ 11.2, J5a±4 ˆ 4.4); 4.25 Bm, 1H, H4); 4.28Bm, 1H, H3); 4.36
Bdd, 1H, H5b, J5a±5b ˆ 11.2, J5b±4 ˆ 2.6); 4.94 Bdd, 1H, H1, J2a±1 ˆ 2.4,
J2b±1 ˆ 5.7); 6.17 Bs, 1H, H50); 7.35 Bm, 6H, HAr); 7.64 Bm, 4H, HAr). 13C
NMR BCDCl3, 100 MHz) d: 17.2 BC-40-CH3); 19.2 BCBCH3)3); 27.0
BCBCH3)3); 41.8BC-2); 55.3 BC-Ar-O CH3); 70.0 BC-5); 72.4 BC-3); 81.9 BC-4);
0
0
104.8BC-1); 105.1 BC-5 ); 127.8to 136.0 BC-Ar); 146.7 BC-4 ); 173.0 BC-20).
1
anomer 2: H NMR BCDCl3, 400 MHz) d: 1.06 Bs, 9H, CBCH3)3); 1.99 Bddd,
1H, H2a, J2a±2b ˆ 13.2 , J2a±1 ˆ 2.0 , J2a±3 ˆ 6.7); 2.10 Bdt, 1H, H2b, J2a±
3
ˆ 13.2, J ˆ 5); 2.22 Bs, 3H, C-40-CH3); 3.24 Bs, 3H, OCH3); 4.13 Bdd, 1H,
2b
H5a, J5a±5b ˆ 10.8, J5a±4 ˆ 6.7); 4.18Bdd, 1H, H5b, J
ˆ 10.8, J5b±4 ˆ 4.7);
5a±5b
4.31 Bm, 1H, H4); 4.47 Bm, 1H, H3); 5.07 Bdd, 1H, H1, J2a±1 ˆ 2.0, J2b±1 ˆ 5.7);
6.18Bs, 1H, H5 0); 7.36 Bm, 6H, HAr); 7.65 Bm, 4H, HAr).13C NMR BCDCl3,
100 MHz) d: 17.9 BC-40-CH3); 19.2 BCBCH3)3); 27.0 BCBCH3)3); 42.1 BC-2);

THIAAZAHETEROCYCLE NUCLEOSIDE ANALOGUES
353
0
55.1 BC-Ar-OCH3); 71.9 BC-5); 73.8BC-3); 84.2 BC-4); 105.1 BC-5 ); 105.6 BC-
10); 127.9 to 135.9 BC-Ar); 146.7 BC-40); 173.7 BC-20).
3-[83-O-tert-Butyldiphenylsilyl)-20-deoxy-b-D-ribofuranosyl]-4-methyl-1,3-
thiazolin-2-one 826). To a solution of 25 B0.150 g, 0.31 mmol) in freshly
distilled acetonitrile B30 mL), was added tert-butyldimethylsilyl tri-
¯uoromethanesulfonate B0.06 mL, 0.31 mmol) dropwise at À20ꢀC under
argon atmosphere. After 1 h of stirring, an additional amount of tert-
butyldimethylsilyl tri¯uoromethanesulfonate B0.06 mL, 0.31 mmol) was
added at 0ꢀC before the addition of tert-butyldiphenylsilyl chloride B0.16 mL,
0.62 mmol). The mixture was stirred for another 6 h. After adding saturated
aqueous solution of sodium hydrogenocarbonate B3 mL), the stirring was
continued for 12h. The solution was diluted with ammonium chloride
B60 mL), then extracted with dichloromethane B2*50 mL). The organic layers
were washed with water B2*50 mL), dried over magnesium sulfate, ®ltered
and concentrated in vacuo. The residue was puri®ed by ¯ash chromato-
graphy on silica gel eluting with ethyl acetate petroleum ether B2=8), to get 26
in 20% yield. 1H NMR BCDCl3; 400 MHz) d: 1.10 Bs, 9H, CBCH3)3); 1.96 Bdd,
0
1H, H20a, J2 a±2 b ˆ 13.1 , J2 a±1 ˆ 5.8); 2.17 Bs, 3H, C4 -CH3); 2.97 Bddd, 1H,
0
0
0
0
H20b, J2 a±2 bˆ13.1 , J2 b±1 ˆ9.5 , J2 b±3 ˆ5.7); 3.19 Bm, 1H, H5 a); 3.63 Bdd, 1H,
0
0
0
0
0
0
0
H50b, J5 a±5 bˆ12.4, J5 b±4 ˆ2.6); 3.90 Bm, 1H, OH); 4.02 Bm, 1H, H4 ); 4.64
0
0
0
0
0
Bm, 1H, H30); 5.75 Bs, 1H, H5); 5.87 Bdd, 1H, H10, J2 a±1 ˆ5.8, J2 b±1 ˆ9.5);
7.40 Bm, 6H, HAr); 7.64 Bm, 4H, HAr). 13C NMR BCDCl3; 100MHz) d: 15.9
BC40-CH3); 19.0 BCBCH3)3); 26.9 BCBCH3)3); 37.5 BC-20); 63.0 BC-50); 74.7
BC-30); 86.3 BC-10); 89.1 BC-40); 97.2 BC-5); 127.8to 135.7 BC-Ar, C-4); 173.8
0
0
0
0
‡
‡
BC-2). MS BCI) BNH3) [M‡H ] ˆ 470; [M‡NH4 ] ˆ 487.
3-85-O-tert-Butyldiphenylsilyl-2,3-O-isopropylidene-a,b-D-ribofuranosyl)-
6-methoxycarbonyl-4H-1,3-thiazin-2,4-dione 829). To a solution of sodium
hydride B60% mineral oil dispersion) B0.1 g, 2.57 mmol) in dry acetonitrile
B5 mL), at 0ꢀC under argon, was added thiazindione 3 B0.33 g, 2.12 mmol).
The mixture was stirred for 15 min and freshly prepared ribofuranosyl
chloride 288 B0.61 g, 1.37 mmol) was added. After 30 min, the mixture was
allowed to warm to room temperature and stirred for another 15 h.p
Water B100 mL) and dichloromethane B2*100 mL) were added. After
extraction, the organic layer was washed with brine, dried over magnesium
sulfate, ®ltered and evaporated in vacuo. The crude product was puri®ed by
¯ash chromatography on silica gel, eluting with petroleum ether=ethyl acet-
ate B8=2), to get an anomeric mixture of 29 in 54% yield Ba, b ratio ˆ 1=1). 1H
NMR BCDCl3; 200 MHz) d: 1.05, 1.082*Bs, 9H, tBu); 1.19, 1.45 2*Bs, 3H,
CMe2); 1.33, 1.55 2*Bs, 3H, CMe2); 3.67±3.83 Bm, 2*2H, H50a, H50b); 3.83,
3.84 2*Bs, 3H, OCH3); 4.20±4.25, 4.65±4.66 Bm, 2*1H, H40); 4.84±4.98
Bm, 3H, 2*H20, H30); 5.07±5.11 Bdd, 1H, H30, J ˆ 1.75 and 6.26); 5.93, 6.30
2*Bd, 1H, H10, J1 ±2 ˆ 1.8and 4.9); 6.95, 7.00 2*Bs, 1H, H5); 7.35±7.41,
0
0

354
ANE ET AL.
7.63±7.69 Bm, 20H, HAr). 13C NMR BCDCl3; 100 MHz) d: 19.1, 19.2
BCBCH3)3); 24.3, 25.3 BMe2C); 25.7, 27.2 BMe2C); 26.8BCB CH3)3); 52.7, 52.8
BOCH3); 64.1, 65.1 BC-50); 80.1, 81.8 BC-20); 84.9, 88.1 BC-40); 81.6, 82.7 BC-30);
87.3, 88.6 BC-10); 114.0, 114.9 BMe2C); 118.3, 119.4 BC-5); 127.5 to 135.6 BC-
Ar); 140.0, 140.7 BC-6); 163.7, 163.8BC-4); 165.5, 165.8BC ˆO ester); 167.0,
‡
‡
168.0 BC-2). MS {BCl , NH4 ), M‡18 ˆ 615}; BEI) M=z B%): 295 B29); 270
B100); 217 B21); 213 B16); 212 B40); 199 B31); 184 B46); 167 B40); 135 B30); 85
B20); 59 B15); 57 B20); 43 B25).
5-Acetyl-3-85-O-tert-butyldiphenylsilyl-2,3-O-isopropylidene-a,b-ribofur-
anosyl)-3,6-dihydro-2H-1,3-thiazin-2-one 830). An anomeric mixture of 30
was obtained by following a similar experimental procedure as mentioned for
1
29, starting from thiazinone 6, in 50% yield Ba=b ratio ˆ 1=3). H NMR
BCDCl3, 200 MHz) d: 1.12 Bs, 9H, tBu); 1.35 Bs, 3H, CMe); 1.51 Bs, 3H, CMe);
2.35 Bs, 3H, CH3CˆO); 3.73 Bdd, 1H, H50a, J5 a±4 ˆ 2.50 and J5 a±5 b ˆ 11.30);
0
0
0
0
3.85 Bd, 2H, H4, J ˆ 2.22); 3.89 Bdd, 1H, H50b, J5 b±4 ˆ 2.80 and J5 a±
0
0
0
ˆ 11.30); 4.36 Bm, 1H, H40); 4.82 Bd, 1H, H30, J3 ±2 ˆ 6.10); 4.94 Bdd, 1H,
0
0
0 0
5 b
H20, J2 ±1 ˆ 4.30 and J3 ±2 ˆ 6.10); 6.5 Bd, 1H, H1 , J1 ±2 ˆ 4.3); 7.42±7.46
Bm, 5H, HAr); 7.65±7.68Bm, 6H, H6, HAr). 13C NMR BCDCl3; 50 MHz) d:
19.0 BCBCH3)3); 23.2 BC-4); 23.8B CH3-C); 24.8B CH3-CˆO); 26.0 BCH3-C);
26.8BCB CH3)3); 65.9 BC-50); 79.5 BC-20); 81.7 BC-30); 83.2 BC-40); 87.3 BC-10);
112.4 BMe2C); 112.8BC-5); 127.6 to 135.6 BC-Ar); 139.1 BC-6); 167.0 BC-2);
0
0
0
0
0
0
‡
‡
194.4 BCˆO). MS {BCI , NH4 M‡18) ˆ 585}; BEI) M=z B%) : 511 B30); 510
B81); 392 B19); 353 B17); 339 B26); 338 B100); 296 B22); 295 B79); 253 B19); 251
B18); 241 B26); 223 B26); 217 B33); 197 B37); 182 B84); 181 B25); 176 B17); 163
B74); 161 B24); 139 B28); 138 B68); 135 B71); 121 B16); 115 B25); 110 B26); 105 B21);
91 B14); 77 B16); 43 B39). Anal. Calcd for C30H37NO6SSi : C, 63.46; H, 6.57;
N, 2.47; S, 5.67; Si, 4.95. Found: C, 63.21; H, 6.53; N, 2.42; S, 5.79; Si, 4.70.
3-85-O-tert-Butyldiphenylsilyl-2,3-O-isopropylidene-a,b-ribofuranosyl)-
4-methyl-2H-1,3-thiazolin-2-one 831). Compound 31 was obtained follow-
ing a similar experimental procedure as mentioned for 29 starting from
thiazolinone 11 in 47% yield. Anomers 31a and 31b were isolated by ¯ash
chromatography on silica gel, eluting with ethyl acetate=petroleum ether
20
1
B3=7), in 1=2 a=bratio. a anomer: [a]D ˆ ‡52.9 BC ˆ 1, CHCl3). H NMR
BCDCl3; 200 MHz) d Bdelta) ˆ 1.07 Bs, 9H, tBu); 1.38Bs, 3H, CMe ); 1.59 Bs,
2
3H, CMe2); 2.27 Bd, 3H, CH3, JCH -CH ˆ 1.06); 3.77 Bdd, 1H, H50a, J5 a±
0
3
ˆ 2.75 and J5 a±5 b ˆ 11.29); 3.86 Bdd, 1H, H50b, J5 b±4 ˆ 3.20 and J5 b±
0
0
0
0
0
40
ˆ 11.29); 4.43-4.46 Bm, 1H, H40); 4.83 Bdd, 1H, H30, J ˆ 1.83 and J2 ±
0
0
5 a
0
0
0
0
0
30
ˆ 6.56); 4.93 Bdd, 1H, H2 , J2 ±1 ˆ 4.27 and J3 ±2 ˆ 6.56); 6.24 Bq, 1H, H4,
J ˆ 1.06); 6.42 Bd, 1H, H10, J1 ±2 ˆ 4.27); 7.38±7.41 and 7.64±7.70 Bm, 10H,
0
0
HAr). 13C NMR BCDCl3; 50 MHz) d: 17.7 BCBCH3)3); 19.2 BCH3); 25.7, 25.9
3 3
BCBCH3)2); 26.8BCBCH ) ); 64.2 BC-50); 80.5 BC-30); 80.8 BC-20); 83.6 BC-40);
101.7 BC-10); 105.4 BC-4); 114.9 BCMe2); 127.6 to 135.6 BC-Ar); 146.9 BC-5);

THIAAZAHETEROCYCLE NUCLEOSIDE ANALOGUES
355
‡
‡
171.8BC-2). MS {CI , NH4 , [M ‡ H] ˆ 526}; BEI) M=z B%): 469 B24); 468
B74); 296 B71); 295 B71); 275 B23); 221 B42); 217 B27); 199 B46); 198B30)197 B47);
183 B21); 181 B20); 163 B31); 161 B81); 140 B19); 135 B100); 129 B24); 116 B18);
20
115 B25); 91 B24); 77 B20); 57 B25); 43 B35); 41 B18). b anomer: [a]D ˆ -4.2
1
BC ˆ 1, CHCl3). H NMR BCDCl3; 200 MHz) d: 1.10 Bs, 9H, tBu); 1.31 Bs,
3H); 1.48Bs, 3H); 2.31 Bd, 3H, J ˆ 1.2); 3.72 Bdd, 1H, H50a, J5 a±4 ˆ 2.8and
0
0
0
J5 a±5 b ˆ 11.1); 3.84 Bdd, 1H, H50b, J5 b±4 ˆ 3.3); 4.28Bt, 1H, H4 ); 4.83 Bdd,
0
0
0
0
1H, H30, J ˆ 0.9 and J3 ±2 ˆ 6.2); 4.93 Bdd, 1H, H2 , J2 ±1 ˆ 4.5 and J2 ±
0
0
0
0
0
0
0
0
0
30
ˆ 6.2); 5.63 Bq, 1H, H-C4, J ˆ 1.2); 6.40 Bd, 1H, H1 , J1 ±2 ˆ 4.5); 7.39±7.69
Bm, 10H, HAr). 13C NMR BCDCl3; 50 MHz) d: 17.5 BCBCH3)3; 19.2 BCH3);
23.7 BMe2C); 25.4 BMe2C); 26.8BCB CH3)3); 65.7BC-50); 79.8BC-2 0); 82.9 BC-30);
89.3 BC-40); 96.0 BC-10); 113.2 BMe2C); 127.8to 135.6 BC-Ar); 146.9 BC-5),
‡
‡
172.6 BC-2). MS {CI , NH4 , [M ‡ H] ˆ 526}; BEI) M=z B%): 469 B33); 468
B100); 296 B33); 295 B49); 275 B20); 221 B31); 217 B26); 199 B41); 198B14); 197
B38); 183 B21); 181 B21); 163 B28); 161 B77); 140 B46); 135 B94); 129 B23); 115
B28); 91 B31); 77 B18). Anal. Calcd for C28H35NO5SSi: C, 63.97; H, 6.71; N,
2.66; S, 6.10; Si, 6.34. Found: C, 63.75; H, 6.72; N, 2.37; S, 5.94; Si, 6.35.
3-82,3-O-Isopropylidene-a,b-D-ribofuranosyl)-6-methoxycarbonyl-4H-1,3-
thiazin-2,4-dione 832).
A solution of 30 B1.1 g, 1.93 mmol) in methanol
B10 mL) was treated with p-toluene sulfonic acid B0.73 g, 3.86 mmol). The
mixture was stirred at room temperature for 6 h. Water B100 mL) and
dichloromethane B2*100 mL) were added. After extraction, the organic layer
was washed with brine B100 mL), dried over magnesium sulfate, ®ltered and
concentrated. The crude product was puri®ed by ¯ash chromatography on
silica gel, eluting with petroleum ether=ethyl acetate B1=1), to get 32a and 32b
20
in 60% yield Ba=b ratio ˆ 1=1). a anomer: [a]D ˆ ‡39.4 BC ˆ 1.00, CHCl3).
1H NMR BCDCl3; 200 MHz) d: 1.32 and 1.45 B2s, 2x3H, CMe2); 2.25 B1H,
0
OH); 3.67±3.78Bm, 2H, H5 a, H50b); 3.86 Bs, 1H, 3H, OCH3); 4.71±4.76 Bm,
1H, H40); 4.82±4.91 Bm, 2H, H20, H30); 6.20±6.23 Bm, 1H, H10); 7.00 Bs, 1H,
H5). 13C NMR BCDCl3; 50 MHz) d: 24.7 and 25.6 BCBCH3)2); 52.9 BOCH3);
63.1 BC-50); 80.3 BC-20); 81.5 BC-30); 85.8 BC-40); 87.8 BC-10); 115.8B CBCH3)2);
118.7 BC-5); 140.7 BC-6); 163.9 BC-4); 165.9 BCˆO ester); 167.5 BC-2). b
20
1
anomer: [a]D ˆ À39.2 BC ˆ 1.00, CHCl3). H NMR BCDCl3; 200 MHz) d:
1.28and 1.51 B2s, 2x3H, CMe ); 2.51 B1H, OH); 3.61±3.80 Bm, 5H, H50a,
2
H50b and OCH3); 4.16±4.21 Bm, 1H, H40); 4.87 Bdd, 1H, H30, J3 ±4 ˆ 3.52, J3 ±
0
0
0
0
0
0
0
0
0
0
20
20
ˆ 6.4); 5.05 Bdd, 1H, H2 , J2 ±3 ˆ 6.4, J2 ±1 ˆ 3.36); 5.86 Bd, 1H, H1 , J1 ±
ˆ 3.36); 6.98Bs, 1H, H5). 13C NMR BCDCl3; 50 MHz) d: 25.5 and 27.4
BCBCH3)2); 53.1 BOCH3); 63.0 BC-50); 80.8 BC-20); 82.0 BC-30); 86.7 BC-40); 88.1
BC-10); 114.6 BCBCH3)2); 120.1 BC-5); 139.7 BC-6); 164.2 BC-4); 165.6 BCˆO
‡
‡
ester); 168.7 BC-2). MS {CI , NH4 , M‡18 ˆ 377}; M=z B%) : 344 B65); 116
B15); 86 B23); 85 B52); 71 B17); 69 B24); 68 B32); 59 B77); 57 B39); 43 B100); 41
B29); 31 B34); 29 B27). BLSIMS with Cs , Positif in Micromasse)-Calcd for
‡
‡
‡
C14H17NO8S: [M ‡ H] ˆ 359.0753 Found: [M ‡ H] ˆ 360.0752.

356
ANE ET AL.
6-Methoxycarbonyl-3-8a,b-D-ribofuranosyl)-4H-1,3-thiazin-2,4-dione
833). Dowex 50X2-200 B0.31 g, 0.86 mmol), previously washed twice with
methanol, was added to the a or b anomer of 32 B88 mg, 0.245 mmol) in
solution in methanol B5 mL). The mixture was stirred at room temperature
for 15h, ®ltered and the resin was washed twice with methanol. The solution
was evaporated in vacuo and the crude product was puri®ed by preparative
TLC, eluting with ethyl acetate, to get the ribosyls 33a or 33b in 65% overall
20
yield. a anomer: [a]D ˆ ‡25,5 BC ˆ 1, MeOH). 1H NMR BCD3OD;
200 MHz) d: 3.63±3.67 Bm, 2H, H50a and H50b); 3.84 Bs, 3H, OCH3); 4.58±
4.63 Bm, 2H, H40, H30); 4.71±4.76 Bm, 1H, H20); 6.19 Bd, 1H, H10, J1 ±
0
ˆ 5.34); 6.96 Bs, 1H, H5). 13C NMR BCD3OD; 50 MHz) d: 45.3 BC-50); 55.1
20
BOCH3); 63.6 BC-20); 64.1 BC-30); 77.9 BC-40); 80.9 BC-10); 112.0 BC-5); 133.2
‡
BC-6); 155.3 BC-4); 159.0 BCˆO ester); 161.7 BC-2). MS {CI, NH4 ,
M‡18 ˆ 337}, BEI), M=z B%) : 246 B15); 189 B15); 188 B46); 160 B15); 133 B40);
132 B44); 117 B26); 116 B23); 114 B17); 101 B15); 86 B15); 85 B83); 74 B18); 73
B100); 60 B32); 59 B32); 58B21); 57 B71); 55 B19); 45 B26); 43 B23); 31 B33); 29
20
B31). b anomer: [a]D ˆ À35,3 BC ˆ 1, MeOH). 1H NMR BCD3OD;
400 MHz) d: 3.65 Bdd, 1H, H50a, J5 a±4 ˆ 5.8and J
ˆ 12); 3.77 Bdd, 1H,
0
0
0
0
5 a±5 b
H50b, J5 b±4 ˆ 3.5 and J5 b±5 a ˆ 12); 3.84 Bs, 3H, OCH3); 3.92±3.94 Bm, 1H,
0
0
0
0
0
H40); 4.32 Bt, 1H, H30, J ˆ 5.57); 4.68Bdd, 1H, H2 , J2 ±1 ˆ 4.1 and
0
0
J2 ±3 ˆ 5.57); 5.74 Bd, 1H, H1 , J1 ±2 ˆ 4.1); 7.01 Bs, 1H, H5). 13C NMR
BCD3OD; 100MHz) d: 44.2 BC-50); 54.3 BOCH3); 62.6 BC-20); 63.4 BC-30); 77.2
BC-40); 80.2 BC-10); 110.8BC-5); 132.3 BC-6); 156.4 BC-4);158.1 BC ˆO ester);
0
0
0
0
0
‡
160.8BC-2). MS {CI, NH 4 , M‡18 ˆ 337}, BEI), M=z B%): 246 B15); 189 B15);
188 B46); 160 B15); 133 B40); 132 B44); 117 B26); 116 B23); 114 B17); 101 B15); 86
B15); 85 B83); 74 B18); 73 B100); 60 B32); 59 B32); 58 B21); 57 B71); 55 B19); 45
‡
B26); 43 B23); 31 B33); 29 B31). BLSIMS with Cs , Positif in Micromasse)-Calcd
‡
‡
for C11H13NO8S: [M ‡ H] ˆ 320.0362. Found: [M ‡ H] ˆ 320.0370.
5-Acetyl-3,6-dihydro-3-8a,b-D-ribofuranosyl)-2H-1,3-thiazin-2-one 834).
A solution of 30 in THF B5 mL) was treated with tetrabutylammonium
¯uoride trihydrate B0.33 g, 1.05 mmol). The mixture was stirred at room
temperature for 2 h and the solvent was evaporated in vacuo. The crude
product was puri®ed by ¯ash chromatography on silica gel, eluting with
petroleum ether=ethyl acetate B1=1). Dowex 50X2-200 B1 g) was washed twice
with methanol and was added to the resulting 3-B20,30-O-isopropylidene-a,b-
ribofuranosyl)-6-acetyl-2H-1,3-thiazin-2-one B0.22 g, 0.67 mmol) in solution
in methanol B10 mL). The mixture was stirred at room temperature for
another 15 h, ®ltered and the resin was washed thoroughly with methanol.
The solution was concentrated in vacuo and the crude product was puri®ed
by ¯ash chromatography on silica gel, eluting with ethyl acetate=methanol
B98=5), to get a, b-anomeric mixture of 34 in 44% overall yield Ba=b
1
ratio ˆ 1=3). a and b anomers: H NMR BCD3OD; 200 MHz) d: 2.55, 2.58
2*Bs, 3H, 2*CH3); 3.84±4.27 Bm, 8H, H50a, H50b and 2*CH2); 4.68Bm, 1H,

THIAAZAHETEROCYCLE NUCLEOSIDE ANALOGUES
357
H40); 4.82 Bm, 1H, H40); 5.13±5.19 Bm, 1H, H30); 05.43 Bd, 1H, H20); 5.65±5.67
Bm, 1H, H30); 5.07 Bd, 1H, H20); 6.28Bd, 1H, H1 , J ˆ 4.6); 6.33 Bd, 1H, H10,
J ˆ 4.8); 7.60, 7.62 2*Bs, 1H, H6). 13C NMR BCD3OD; 50 MHz) d: 21.0
BCH3); 23.3 BCH3); 25.4 BC-4); 26.1 BC-4); 63.3, 63.5 BC-50); 79.0, 79.2 BC-20);
81.2 BC-30); 81.3 BC-30); 83.0 BC-40); 87.0 BC-10); 86.6 BC-40); 87.4 BC-10); 113.5,
113.4 BC-5); 139.5 BC-6); 167.8, 169.1 BC-2); 194.6 BCˆO). BLSIMS with Cs‡,
‡
Positif in Micromasse)-Calcd for C11H15NO6S: [M ‡ H] ˆ 290.0698. Found:
‡
[M ‡ H] ˆ 290.0698.
3-82,3-O-Isopropylidene-a,b-D-ribofuranosyl)-4-methyl-2H-1,3-thiazolin-
2-one 835). A solution of 31a or 31b B0.5 g, 0.95 mmol) in THF B5 mL) was
treated with tetrabutylammonium ¯uoride trihydrate B0.36 g, 1.1 mmol). The
mixture was stirred at room temperature for 2 h. and the solvent was eva-
porated in vacuo. The crude product was puri®ed by ¯ash chromatography
on silica gel, eluting with petroleum ether=ethyl acetate B1=1), to get 35a or
20
1
35b in 70% yieds. a anomer: [a]D ˆ ‡39.4 BC ˆ 0.62, CHCl3). H NMR
BCDCl3; 200 MHz) d: 1.32 and 1.45 B2s, 2*3H, CMe2); 2.25 B1H, OH); 3.67±
3.78Bm, 2H, H5 a, H50b); 3.86 Bs, 1H, 3H, OCH3); 4.71±4.76 Bm, 1H, H40);
0
4.82±4.91 Bm, 2H, H20, H30); 6.20±6.23 Bm, 1H, H10); 7.00 Bs, 1H, H5). 13C
NMR BCDCl3; 50 MHz) d: 24.7 et 25.6 BCBCH3)2); 52.9 BOCH3); 63.1 BC-50);
80.3 BC-20); 81.5 BC-30); 85.8 BC-40); 87.8 BC-10); 115.8B CBCH3)2); 118.7 BC-5);
140.7 BC-6); 163.9 BC4ˆO); 165.9 BCˆO ester); 167.5 BC2ˆO). b anomer:
20
1
[a]D ˆ À30.5 BC ˆ 0.76, CHCl3). H NMR BCDCl3; 200 MHz) d: 1.28and
1.51 B2s, 2*3H, CMe2); 2.51 B1H, OH); 3.61±3.80 Bm, 5H, H50a, H50b, OCH3);
4.16±4.21 Bm, 1H, H40); 4.87 Bdd, 1H, H30, J3 ±4 ˆ 3.52, J3 ±2 ˆ 6.4); 5.05 Bdd,
0
0
0
0
1H, H20, J2 ±3 ˆ 6.4, J2 ±1 ˆ 3.36); 5.86 Bd, 1H, H1 , J1 ±2 ˆ 3.36); 6.98Bs, 1H,
H5). 13C NMR BCDCl3; 50 MHz) d: 25.5 and 27.4 BCBCH3)2); 53.1 BCH3O);
63 BC-50); 80.8 BC-20); 82 BC-30); 86.7 BC-40); 88.1 BC-10); 114.6 BCBCH3)2);
120.1 BC-5); 139.7 BC-6); 164.2 BC4ˆO); 165.6 BCˆO ester); 168.7 BC2ˆO).
0
0
0
0
0
0
0
‡
‡
MS {CI , NH4 , M‡18 ˆ 377}; M=z B%): 344 B65); 116 B15); 86 B23); 85 B52);
71 B17); 69 B24); 68B32); 59 B77); 57 B39); 43 B100); 41 B29); 31 B34); 29 B27).
BLSIMS with Cs , Positif in Micromasse)-Calcd for C14H17NO6S:
‡
‡
‡
[M ‡ H] ˆ 359.0753. Found: [M ‡ H] ˆ 360.0752.
4-Methyl-3-8a,b-ribofuranosyl)-2H-1,3-thiazolin-2-one
836). Dowex
50X2-200 B0.31g, 0.86 mmol), previously washed twice with methanol, was
added to the a or b anomer of ꢀ35) B88 mg, 0.245 mmol) in solution in
methanol B5 mL). The mixture was stirred at room temperature for 15 h,
®ltered and the resin was washed twice with methanol. The solution was
evaporated in vacuo and the crude product was puri®ed by preparative TLC
eluting with ethyl acetate to get the ribosyls 36a or 36b in 72% yields. d
20
anomer: [a]D ˆ ‡25,5 BC ˆ 1, MeOH). 1H NMR BCDCl3; 200 MHz) d: 2.24
Bs, 3H, CH3); 3.60±3.86 Bm, 2H, H50a, H50b); 4.39±4.42 Bm, 1H, H40);
4.70±4.81 Bm, 2H, H20, H30); 6.20 Bd, 1H, H10, J ˆ 3.6); 6.25 Bs, 1H, H4). 13C

358
ANE ET AL.
NMR BCDCl3; 50 MHz) d: 17.7 BCH3); 62.4 BC-50); 79.3 BC-20); 80.2 BC-30);
0
83.6 BC-40); 100.8BC-1 ); 105.5 BC-4); 146.0 BC-5); 173.2 BC-2). b anomer:
[a]D ˆ À12,3 BC ˆ 1, MeOH). 1H NMR BCDCl3; 200 MHz) d: 2.10 Bd, 3H,
20
CH3, JCH
-
CH
ˆ 1.1); 3.58±3.76 Bm, 2H, H50, H50b); 4.20±4.24 Bm, 1H, H40);
3
4.90 Bdd, 1H, H30, J3 ±4 ˆ 2.96, J3 ±2 ˆ 6.1); 5.20 Bdd, 1H, H2 , J2 ±1 ˆ 2.29,
0
0
0
0
0
0
0
0
0
0
0
0
J3 ±2 ˆ 6.1); 5.40 Bd, 1H, H1 , J2 ±1 ˆ 2.29); 5.70 Bq, 1H, H4, JCH-CH ˆ 1.1).
3
13C NMR BCDCl3; 50 MHz) d: 15.8BCH ); 63.0 BC-50); 81.2 BC-20); 82.4
3
BC-30); 86.5 BC-40); 91.6 BC-10); 98.0 BC-4); 132.0 BC-5); 173.9 BCˆO). BLSIMS
‡
‡
with Cs , Positif in Micromasse) -Calcd for C9H13NO5S: [M ‡ H] ˆ
‡
247.0514. Found: [M ‡ H] ˆ 247.0536.
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Received October 5, 2001
Accepted April 30, 2002