Sugar-Modified Uridine Bisvinyl Sulfone: Synthesis of a Bifunctionalized Nucleoside Michael Acceptor and Its Use in Stereoselective Tandem Cyclization

Article abstract of DOI:10.1021/jo9705576

A bisvinyl sulfone functionality is incorporated into the carbohydrate moiety of uridine to synthesize 6 (or 7) which is a bifunctionalized nucleoside Michael acceptor and has the potential to form covalent bond with biological nucleophiles. This compound could be used to generate a large number and a new class of bicyclic S,S-dioxidethiazine derivatives 8-12 in stereoselective fashion. Compound 6 is also useful for the synthesis of a wide variety of monosubstituted compounds 13-15. The structures of compounds 8-12 have been established unambiguously by synthesising the core structure 28 in a stereospecific fashion.

Full text of DOI:10.1021/jo9705576

1754
J . Org. Chem. 1998, 63, 1754-1760
Articles
Su ga r -Mod ified Ur id in e Bisvin yl Su lfon e: Syn th esis of a
Bifu n ction a lized Nu cleosid e Mich a el Accep tor a n d Its Use in
Ster eoselective Ta n d em Cycliza tion †
Sanjib Bera,‡ Graham J . Langley,§ and Tanmaya Pathak*,‡,|
Organic Chemistry Division (Synthesis), National Chemical Laboratory, Pune 411 008, India, and
Department of Chemistry, The University, Southampton SO9 5NH, UK
Received March 25, 1997
A bisvinyl sulfone functionality is incorporated into the carbohydrate moiety of uridine to synthesize
6 (or 7) which is a bifunctionalized nucleoside Michael acceptor and has the potential to form covalent
bond with biological nucleophiles. This compound could be used to generate a large number and
a new class of bicyclic S,S-dioxidethiazine derivatives 8-12 in stereoselective fashion. Compound
6 is also useful for the synthesis of a wide variety of monosubstituted compounds 13-15. The
structures of compounds 8-12 have been established unambiguously by synthesising the core
structure 28 in a stereospecific fashion.
In tr od u ction
could be used as a synthon6 to produce new classes of
bicyclic nucleosides by reacting it with appropriate nu-
cleophiles. Synthesis of such carbohydrate-modified
polycyclic nucleosides is of immense importance. Natu-
rally occurring bicyclic nucleosides, such as griseolic
acids, are known to inhibit nucleotide-phosphodiesterase.7
Herbicidines and aureonucleomycin are the unusual
nucleosides having furano-pyrano-pyran skeletons.8
Synthesis of various polycyclic nucleosides has also
gained momentum in recent years, either for controlling
the conformational mobilities of the corresponding nucle-
otides incorporated in the DNA9 or to use the modified
nucleosides as HIV reverse transcriptase inhibitors.10
Vinyl sulfones inhibit1 the action of glyceraldehyde-3-
phosphate dehydrogenase and vinyl sulfone containing
dipeptides have been shown2 to be efficient inhibitors of
cystein protease. Attempts have been made3 in the
recent past to synthesize chemically reactive analogues
of AZT that may form a covalent bond to viral reverse
transcriptase. Since vinyl sulfones, highly reactive
Michael acceptors,4 reportedly1,2 show their activities by
forming covalent bonds with biological nucleophiles, we
decided to incorporate5 vinyl sulfone functionality at the
carbohydrate moieties of nucleosides. After studying5 the
reactivities of 3′-deoxy-3′-S-vinylsulfonylthymidine 16
with various nucleophiles, we envisaged that modified
nucleosides equipped with a bisvinyl sulfone functional
group would also have the potential to form covalent
linkages with biological nucleophiles since bisvinyl sul-
fone has also been reported1 to be an efficient enzyme
inhibitor.
(6) For the use of bisvinyl sulfone in the synthesis of various
heterocycles, see: (a) Arya, V. P. Ind J . Chem. 1975, 13, 1262. (b)
Minbaev, B. U.; Shostakovskii, M. F.; Kagarlitskii, A. D. Khim.
Geterotsikl. Soedin. 1983, 1199. Chem. Abstr. 100, 6422u. (c) Nagao,
Y.; Sakurai, H. Chem. Lett. 1976, 379. (d) Kropf, H.; Bernert, C.-R.
J ustus Liebigs Ann. Chem. 1951, 793, 151.
(7) Tulshian, D.; Doll, R. J .; Stansberry, M. F.; McPhail, A. T. J .
Org. Chem. 1991, 56, 6819.
(8) Emery, F.; Vogel, P. J . Org. Chem. 1995, 60, 5843.
(9) (a) Tarkoy, M.; Bolli, M.; Schweizer, B.; Leumann, C. Helv. Chim.
Acta 1993, 76, 481. (b) Tarkoy, M.; Leumann, C. Angew. Chem., Int.
Ed. Engl. 1993, 32, 1432. (c) J ones, R. J .; Swaminathan, S.; Milligan,
J . F.; Wadwani, S.; Froehler, B. C.; Matteucci, M. D. J . Am. Chem.
Soc. 1993, 115, 9816. (d) Tarkoy, M.; Bolli, M.; Leumann, C. Helv.
Chim. Acta 1994, 77, 716. (e) Matteucci, M. D.; Zou, R. Tetrahedron
Lett. 1996, 37, 941. (f) Haly, B.; Bharadwaj, R.; Sanghvi, Y. S. Synlett
1996, 687. (g) Yannopoulos, C. G.; Zhou, W. Q.; Nower, P.; Peoch, D.;
Sanghvi, Y. S.; J ust, G. Synlett 1997, 378. (h) Nielsen, P.; Pfundheller,
H. M.; Wengel, J . Chem. Commun. 1997, 825.
(10) (a) Altmann, K. H.; Imwinkelried, R.; Kesseiring, R.; Rihs, G.
Tetrahedron Lett. 1994, 35, 7625. (b) Rong, J .; Roselt, P.; Plavec, J .
Chattopadhyaya, J . Tetrahedron 1994, 50, 5273. (c) Garg, N.; Hossain,
N.; Chattopadhyaya, J . Tetrahedron 1994, 50, 5273. (d) Grangier, G.;
Aitken, D. J .; Guillaume, D.; Husson, H.-P. Tetrahedron Lett. 1994,
35, 4355. (e) Chang, H. S.; Bergmeir, S. C.; Frick, J . A.; Bathe, A.;
Rapoport, H. J . Org. Chem. 1994, 59, 5336. (f) Ezzitouni, A.; Barchi,
J . J . J r.; Marquez, V. E. J . Chem. Soc. Chem. Commun. 1995, 1345.
(g) Chao, Q.; Nair, V. Tetrahedron Lett. 1995, 36, 7375. (h) J eong, L.
S.; Marquez, V. E. Tetrahedron Lett. 1996, 37, 2353. (i) Endova, M.;
Masojidkova, M.; Budesinsky, M.; Rosenberg, I. Tetrahedron Lett. 1996,
37, 3497. (j) Chao, Q.; Nair, V. Tetrahedron 1997, 53, 1957. (k)
Ezzitouni, A.; Marquez, V. E. J . Chem. Soc., Perkin Trans. 1 1997,
1073.
In addition to above-mentioned properties, the parent
nucleoside 6 (or 7) will be able to generate a wide range
of reactive nucleosides in partially derivatized forms and
† NCL communication no. 6423.
‡ National Chemical Laboratory.
§ The University, Southampton.
| Present address: Department of Organic Chemistry, University
of Karlsruhe, Richard-Willstatter-Allee 2, D-76128 Karlsruhe, Ger-
many.
(1) Dai Eun, S.; Sung, C.; Yun Bae, K.; Yong Han, L.; Seung Hee,
K. Biochem. Biophys. Res. Commun. 1993, 195, 1224.
(2) Palmer, J . T.; Rasnick, D.; Klaus, J . L.; Bromme, D. J . Med.
Chem. 1995, 38, 3193.
(3) Schreiber, S. L.; Ikemoto, N. Tetrahedron Lett. 1988, 29, 3211.
(4) Simpkins, N. S. Sulphones in Organic Synthesis; Pergamon
Press: Oxford, 1993.
(5) Bera, S.; Sakthivel, K.; Langley, G. J .; Pathak, T. Tetrahedron
1995, 51, 7857.
S0022-3263(97)00557-4 CCC: $15.00 © 1998 American Chemical Society
Published on Web 02/26/1998

Sugar-Modified Uridine Bisvinyl Sulfone
J . Org. Chem., Vol. 63, No. 6, 1998 1755
Sch em e 1
Moreover, synthesis of this new class of bicyclic nucleo-
sides equipped with S,S-dioxide moiety will be interesting
as several heterocycles containing this functionality, as
part of the ring, have been synthesized. For example,
1-O-acetyl-2,3,4,6-tetra-O-methyl-5-thio-R-D-glucopyra-
nose S,S-dioxide,11 an analogue of 1-O-acetylglucopyra-
nose; a thiadiazine S,S-dioxide diacyclonucleoside;12 and
the sulfone of 4′-thiothymidine13 have been synthesized
to study their biological and biophysical properties.
2,2′-O-anhydro bridge was hydrolyzed by aqueous NaOH
treatment to produce 3 in 96% yield. Oxidation of 3 with
magnesium monoperphthalate (MMPP) produced 3′-
deoxy-3′-S-(2-hydroxyethylsulfonyl)-5′-O-trityl-ara-uri-
dine 5 in 86% yield. Both the hydroxyl groups of 5 were
mesylated and the crude product obtained after workup
was heated at 40 °C in pyridine; elimination of the
mesylates produced the desired bisvinylsulfonyl uridine
6 in 86% yield (Scheme 1). Detritylation of compound 6
with 80% aqueous acetic acid produced compound 7;
however, for the sake of convenience, crude 7 (after
removing tritanol by triturating the detritylating mixture
of 6 with ether) was treated directly with nucleophiles.
The products were isolated as the corresponding benzoy-
lated derivatives.
Rea ction s of 6 a n d 7 w ith Nu cleop h iles. Com-
pounds 6 and 7 were reacted with six primary amines in
methanol. All amines except allylamine were slow to
react (around 2 days at room temperature), but the
reactions15 produced bicyclic derivatives 8-12 in high
yields in stereoselective fashion (Scheme 2). Structures
of all compounds were established unambiguously through
alternative synthesis (see later text). To the best of our
knowledge, this group of bicyclic thiazine derivatives is
the first of its kind in the literature. One equivalent of
p-anisidine reacted with 7 to produce a single compound.
Attempted cyclization of this compound was unsuccessful,
even at elevated temperature. The product was isolated
as its dibenzoyl derivative 13. Morpholine and dimethyl
malonate/sodium hydride, reacted16 with 6 to produce 14
Resu lts a n d Discu ssion
Syn t h esis of 5′-O-Tr it yl-2′,3′-d id eoxy-2′-en e-3′-S-
(1-vin ylsu lfon yl)u r id in e 6. 5′-O-Trityl-2′,3′-O-anhy-
dro-lyxo-uridine 114 was reacted with mercaptoethanol
in the presence of TMG to generate a mixture of 2′-deoxy-
2′-S-(2-hydroxyethylthio)-5′-O-trityl-xylo-uridine 2 and 3′-
deoxy-3′-S-(2-hydroxyethylthio)-5′-O-trityl-ara-uridine 3.
As all efforts to separate the isomers failed, the primary
hydroxyl group of the hydroxyethylthio moieties of 2 and
3 were benzoylated selectively at 0 °C. After workup,
2′(3′)-hydroxyl groups of the crude benzoylated products
were mesylated at 0 °C. The resulting mesylated prod-
ucts were heated at 100 °C in pyridine; intramolecular
2′,3′-epithiiranium ion formation followed by the attack
of C-2 oxygen at the C-2′ center resulted in the formation
of the 2,2′-O-anhydro derivative 4 in 50% overall yield
in four steps. Compound 4 was debenzoylated and the
(11) Yuasa, H.; Takenaka, A.; Hashimoto, H. Bull. Chem. Soc. J pn.
1990, 63, 3473.
(12) Esteban, A. I.; J uanes, O.; Marz, A.; Conde, S. Tetrahedron
1994, 50, 13865.
(13) Lousi Hancox, E.; Hamor, T. A.; Walker, R. T. Tetrahedron Lett.
1994, 35, 1291.
(15) Selection of solvent was important for these reactions. For
example, when 6 was reacted with isobutylamine in chloroform no
cyclized product was obtained.
(14) Bera, S.; Pathak, T.; Langley, G. J . Tetrahedron 1995, 51, 1459.
(16) Bera, S. Ph.D. Thesis, University of Poona, Pune, India, 1997.

1756 J . Org. Chem., Vol. 63, No. 6, 1998
Bera et al.
Sch em e 2
Sch em e 4
Sch em e 3
hydroxyl group of 3 with TBDMS to produce 19 in 93%
yield. Compound 19 was oxidized to 20. Compound 21
was obtained by mesylating 20 and heating the reaction
mixture at 40 °C. On reaction with benzylamine in
dichloromethane, 21 generated 22 exclusively in 79%
yield.19 Deprotection of 22 produced 23. All attempts
to cyclize 23 were unsuccessful (Scheme 4). However,
23 was needed for cross-checking the structure of 29.
Since 23 could not be cyclized, we turned our attention
to the synthesis of 29. We expected that by having both
C-2′-N and C-3′-S bonds in R configurations, the cy-
clization of 29 would be easier than that of 23. For the
synthesis of 29 we started with the anhydro derivative
4, as it was having the desired configurations at both the
C-2′ and C-3′ positions. The C-3′-S linkage in 4 was
already R due to the opening of lyxo-epoxide 1 by
mercaptoethanol from the R face. The 2,2′-O-anhydro
linkage, on the other hand, would allow a nucleophile,
such as azide, to attack the C-2′ position exclusively from
the R side. Compound 24 was thus obtained by the
azidolysis of 4 at elevated temperature in 70% yield.
Debenzoylation of 24 produced 25. Compound 25 was
oxidized to the sulfone derivative 26 in high yield. The
presence of the azido group in 24, 25, and 26 was
confirmed by the appearance of sharp peaks at 2130,
2140, and 2125 cm-1, respectively in the IR spectra. The
azido group of 26 was reduced and the crude amino
derivative 27 was cyclized under Mitsonubo conditions.20
and 15 in 92 and 86% yields, respectively. All these
reactions (Scheme 3) demonstrated that the exocyclic
vinyl sulfone group of 6 or 7 was more reactive than the
endocyclic one.
Str u ctu r a l Elu cid a tion . To establish the structures
of 8-12 unambiguously, we decided to synthesize some
of these compounds through different routes. The most
important requirement of such a synthesis would be
regio- and stereospecific construction of C-2′-N and
C-3′-S bonds. We assumed that in the case of 8-12,
the C-2′-N bond was R to the plane of the furan ring
because it was demonstrated earlier17 that nucleophiles
attacked C-2′ of 1-(5-O-trityl-2,3-dideoxy-3-toluenesulfo-
nyl-â-D-glyceropent-2-enofuranosyl)uracil (and adenosine)
exclusively from the R-side due to the presence of a bulky
heterocycle at the C-1′ position in the â configuration. It
was also known that intermolecular Michael type addi-
tion of thiophenol to 1-p-tolylsulfonylcyclopentene18 and
benzylamine to nucleosides17 equipped with endocyclic
vinyl sulfone functionalities exclusively produced the
trans product due to steric strain. Compound 21, with
only one vinyl sulfone group available for reaction was,
therefore, selected as the key starting material for
producing C-2′-NR and C-3′-Sâ linkages. Synthesis of
21 began with the selective protection of the primary
(19) This reaction also demonstrated that by using
a system
represented by 21, it would be possible to incorporate various func-
tionalities preferentially into the endocyclic vinyl sulfone moiety of
nucleosides. The exocyclic vinyl sulfone functionality may be generated
later from compound 23. This methodology will produce a wide variety
of partially functionalized vinyl sulfone derivatives.
(17) Wu, J .-C.; Pathak, T.; Tong, W.; Remaud, G.; Chattopadhyaya,
J . Tetrahedron 1988, 44, 6705.
(18) Truce, W. E.; Levy A. J . J . Org. Chem. 1963, 28, 679.
(20) Mitsunobu, O. Synthesis 1981, 1.

Sugar-Modified Uridine Bisvinyl Sulfone
J . Org. Chem., Vol. 63, No. 6, 1998 1757
Sch em e 5
Sch em e 6
respectively. These values compared well with the same
methylene carbons of 17 (51.8 ppm when X ) morpholi-
nyl; 49.4 ppm when X ) dimethylmalonatyl).5
Research is currently in progress to extend the present
observations in the area of carbohydrates and to use the
bisvinyl sulfone modified nucleosides as building blocks
in the synthesis of backbone-modified oligonucleotides.
Exp er im en ta l Section
Gen er a l In for m a tion . See refs 5 and 14.
5′-O-Tr ityl-2,2′-O-a n h yd r o-3′-d eoxy-3′-S-(2-O-ben zoyl-
eth yl)u r id in e 4. To a solution of mercaptoethanol (3.9 g, 50
mmol) in DMF (25 mL), TMG (1,1,3,3-tetramethylguanidine)
(2.3 g, 20 mmol) was added and the mixture was heated at 70
°C for 10 min. To this mixture, epoxide 114 (4.68 g, 10 mmol)
was added and the reaction mixture was heated at 70 °C for
2 h. It was then cooled to room temperature and poured into
saturated NaHCO3 solution with vigorous stirring. The
mixture was filtered and the residue was washed with water
and dissolved in EtOAc. The EtOAc part was dried over Na2-
SO4 and filtered. The filtrate was evaporated to dryness and
the solid residue was purified over silica gel. This purified
mixture of isomers 2 and 3 (8.5 mmol) was dissolved in
pyridine (40 mL) and cooled at 0 °C. Benzoyl chloride (1.4 g,
9.5 mmol) in pyridine (20 mL) was added dropwise for a period
of 1 h. After the consumption of the starting material (TLC),
the reaction mixture was poured into saturated NaHCO3
solution with stirring. The residue was filtered, washed with
water and then dissolved in EtOAc. The EtOAc solution was
dried over anhydrous Na2SO4 and filtered. The filtrate was
evaporated to dryness. The crude monobenzoylated product
was dissolved in pyridine (40 mL) and mesyl chloride (2.86 g,
25 mmol) in pyridine (10 mL) was added dropwise at 0 °C.
After the completion of addition, the reaction mixture was kept
at 4 °C overnight. The reaction mixture was then poured into
saturated NaHCO3 solution. The residue was filtered, washed
with water, dried, and dissolved in EtOAc. The EtOAc solution
was dried over Na2SO4 and filtered. The filtrate was evapo-
rated to dryness. The solid residue was then dissolved in
anhydrous pyridine (75 mL) and heated at 100 °C for 26 h.
The reaction mixture was then cooled to room temperature
and poured into saturated NaHCO3 solution. The residue was
filtered, washed with water, air-dried, and dissolved in EtOAc.
The EtOAc part was dried over anhydrous Na2SO4 and filtered.
The filtrate was evaporated to dryness. The white residue was
purified over silica gel to produce compound 4 (3.16 g, 50%,
for four steps). Mp: 74-76 °C. 1H NMR (CDCl3): δ 8.02 (m,
2H), 7.61-7.19 (m, 19H), 6.15 (d, 5.8 Hz, 1H), 5.98 (d, 7.6 Hz,
1H), 5.31 (m, 1H), 4.50 (t, 2H), 4.26 (q, 1H), 3.71 (m, 1H), 3.11
(d, 5.6 Hz, 2H), 3.02 (m, 2H). 13C NMR (CDCl3): δ 171.6,
166.2, 159.2, 143.2, 134.8, 133.3, 129.7, 128.6, 128.4, 128.1,
127.4, 110.3, 90.5, 88.9, 87.1, 86.2, 63.3, 49.4, 31.0. HRMS
(EI, M+): for C37H32N2O6S calcd 632.1981, obsd 632.1946.
1-[5-O-Tr ityl-3-deoxy-3-S-(2-h ydr oxyeth yl)-â-D-a r a -fu r a-
n osyl]u r a cil 3. To a solution of 4 (3.16 g, 5 mmol) in EtOH
(40 mL) and water (10 mL), was added 1 N NaOH (15 mL)
solution. The reaction mixture was stirred at room temper-
ature. After 2 h, the reaction mixture was neutralized with 1
N HCl solution under cold conditions. The residue thus
obtained was filtered, washed with water, air-dried, and
dissolved in EtOAc. The EtOAc solution was dried over
anhydrous Na2SO4 and filtered. The filtrate was evaporated
to dryness and the white residue was purified over silica gel
to give 3 (2.62 g, 96%). Mp: 99-100 °C. 1H NMR (CDCl3): δ
8.18 (d, 8.2 Hz, 1H), 7.46-7.25 (m, 15H), 6.15 (d, 5.9 Hz, 1H),
5.33 (d, 8.1 Hz, 1H), 4.55 (t, 1H), 3.84-3.39 (m, 7H), 2.77 (m,
2H). 13C NMR (CDCl3): δ 164.6, 151.6, 143.4, 142.1, 129.0,
The required S,S-dioxide thiazine derivative 28 was
obtained in 80% yield. In an attempt to synthesize 9,
27 was benzylated21 in 40% yield. The cyclization of 29,
like the cyclization of its isomer 23 was also unsuccessful
(Scheme 5). However, compound 9 was debenzylated in
75% yield by reacting it with 4% formic acid and Pd/C in
refluxing methanol. The debenzylated product of 9 was
identical to the thiazine derivative 28. Furthermore, 28
on treatment with allyl bromide in the presence of silver
oxide produced previously synthesized allyl derivative 10
(Scheme 6). These experiments proved unambiguously
that the bicyclic derivatives 8-12 were cis-fused.
The structures of 13-15 were established very easily
by comparing their spectroscopic signals with those of
16, 17, or 18.5 In all cases, proton signals at around 6.8
ppm (H-2′) were present, whereas the characteristic
signal of the methylene group of the vinyl sulfone
function (6.42 ppm for 16)5 was absent. Moreover, the
signals at 5.78 ppm (for 6) characteristic of SO2CH of the
vinyl sulfone group (6.13 ppm in case of 16)5 was also
1
absent in the H NMR spectra16 of 13-15. On the other
hand, methylene carbons16 attached to the sulfone groups
of 13, 14, and 15 appeared at 52.8, 51.6, and 52.3 ppm,
(21) Celewiz, L.; Urjasz, W.; Golankiwick, K. Nucleosides Nucleotides
1994, 12, 951.

1758 J . Org. Chem., Vol. 63, No. 6, 1998
Bera et al.
128.2, 127.6, 101.8, 87.7, 85.0, 81.5, 78.2, 62.1, 61.6, 47.7, 34.8.
HRMS (EI, M+) for C30H30N2O6S calcd 546.1825, obsd 546.1778.
1-[5-O-Tr it yl-3-d eoxy-3-S-(2-h yd r oxyet h ylsu lfon yl)-â-
D-a r a -fu r a n osyl]u r a cil 5. To a solution of 3 (1.63 g, 3 mmol)
in MeOH (30 mL) was added MMPP (4.5 g, 9 mmol) and the
reaction mixture was stirred at room temperature for 4-5 h.
The white residue was filtered and washed with MeOH. The
filtrate was evaporated to dryness under reduced pressure. The
residue was triturated with saturated NaHCO3 solution and
filtered. The residue was washed with NaHCO3 solution
followed by water and dried. The solid mass was then
dissolved in EtOAc, dried over Na2SO4, and filtered. The
filtrate was evaporated to dryness and the white residue was
purified over silica gel to give 5 (1.49 g, 86%). Mp: 154-155
°C. 1H NMR (CDCl3 + DMSO-d6): δ 7.58 (d, 8.1 Hz, 1H),
7.27-7.03 (m, 15H), 5.91 (d, 5.4 Hz, 1H), 5.74 (d, 1H), 5.03 (d,
8.1 Hz, 1H), 4.63 (m, 2H), 4.30 (m, 1H), 4.06 (m, 1H), 3.84 (m,
2H), 3.45-2.94 (m, 4H). 13C NMR (CDCl3 + DMSO-d6): δ
162.5, 149.4, 142.3, 140.7, 127.4, 126.7, 126.0, 99.3, 85.7, 84.1,
73.2, 70.1, 66.8, 62.8, 54.2, 54.1. HRMS (EI, M+) for
1-[5-O-Tr it yl-2,3-d id eoxy-2-N-a llyl-4H-2,3,5,6-t et r a h y-
d r o-1,4-th ia zin e-1,1-d ioxid es-â-D-r ibo-fu r a n osyl]u r a cil 10
(0.22 g, 73%). Mp: 135-137 °C. 1H-1H COSY NMR
(CDCl3): δ 7.94 (d, 8.2 Hz, 1H) H-6; 7.43-7.27 (m, 15H) trityl;
6.27 (d, 4.8 Hz, 1H) H-1′; 5.76 (m, 1H) dCH; 5.21 (m, 3H)
dCH2, H-5; 4.76 (m, 1H) H-4′; 3.85-3.49 (m, 6H) H-2′, H-3′,
H-5′, H-5′′, SO2CH2; 3.13 (m, 4H) CH2NCH2. 13C NMR
(CDCl3): δ 163.7, 150.5, 142.9, 139.9, 134.2, 128.8, 128.3, 127.7,
118.8, 102.6, 88.3, 83.9, 76.1, 68.2, 63.6, 58.8, 57.3, 47.9, 47.3.
HRMS (EI, M+) for C33H33N3O6S calcd. 599.2090, obsd 599.2081.
Gen er a l P r oced u r e for th e Syn th esis of 11-13.
A
solution of 6 (0.73 mmol) in 80% aqueous HOAc (50 mL) was
heated at 75 °C for 45 min. HOAc was removed under reduced
pressure and the residual HOAc was coevaporated with EtOH.
The solid residue was triturated with ether. The detritylated
product 7 was dissolved in MeOH (15 mL). Appropriate amine
(0.73 mmol) was added to the mixture. The suspension was
stirred at room temperature for 22-72 h. MeOH was removed
under reduced pressure. The residue was dissolved in anhy-
drous pyridine (15 mL) and benzoyl chloride (0.75 g, 5 mmol)
was added dropwise at 0 °C. The reaction mixture was stirred
at 0 °C. After 2 h the mixture was poured into saturated
NaHCO3 solution (60 mL) and extracted with chloroform (3 ×
20 mL). The chloroform part was evaporated to dryness and
the residual pyridine was coevaporated with toluene. The
product was purified over silica gel.22
C
30H30N2O8S calcd 578.1723, obsd 578.1672.
1-[5-O-Tr ityl-2,3-d id eoxy-3-S-(vin ylsu lfon yl)-â-D-glyc-
er op en t-2-en ofu r a n osyl]u r a cil 6. Compound 5 (1.15 g, 2
mmol) was dissolved in pyridine (20 mL), and mesyl chloride
(1.4 g, 12 mmol) in pyridine (5 mL) was added dropwise at 0
°C. After the addition, the reaction mixture was left at 4 °C
overnight. It was then poured into saturated NaHCO3 solution
(50 mL) and extracted with dichloromethane (3 × 20 mL). The
dichloromethane part was evaporated to dryness under re-
duced pressure and the residue was coevaporated with toluene.
The brown residue was partitioned between EtOAc (80 mL)
and water (70 mL). The EtOAc part was dried over anhydrous
Na2SO4 and filtered. The filtrate was evaporated to dryness
under reduced pressure. The residue was dissolved in anhy-
drous pyridine (30 mL) and heated at 40 °C for 1.5 h. The
solution was poured into saturated NaHCO3 solution (100 mL)
and extracted with dichloromethane (3 × 25 mL). The
dichloromethane part was evaporated and the residual pyri-
dine was coevaporated with toluene under reduced pressure.
The residue was purified over silica gel to give 6 (0.93 g, 86%).
Mp:195-198 °C. 1H-1H COSY NMR (CDCl3): δ 9.10 (bs, 1H)
NH; 7.90 (d, 8.0 Hz, 1H) H-6; 7.68-7.24 (m, 15H) trityl; 7.15
(m, 1H) H-1′; 6.80 (bs, 1H) H-2′; 6.52-6.23 (m, 2H) dCH2; 5.78
(d, 9.2 Hz, 1H) SO2CH; 5.16 (m, 1H) H-4′; 4.65 (d, 8.1 Hz, 1H)
H-5; 3.83 (m, 1H), 3.66 (m, 1H) H-5′, H-5′′. 13C NMR (CDCl3
+ DMSO-d6): δ 163.4, 150.8, 146.1, 142.9, 141.2, 138.5, 136.8,
131.4, 129.1, 128.1, 127.6, 102.3, 88.1, 87.7, 83.7, 63.3. HRMS
(EI, M+) for C30H26N2O6S calcd 542.1512, obsd 542.1467.
1-[5-O-Ben zoyl-2,3-d id eoxy-2-N-(2-O-ben zoyleth yl)-4H-
2,3,5,6-tetr a h yd r o-1,4-th ia zin e-1,1-d ioxid es-â-D-r ibo-fu r a -
n osyl]u r a cil 11 (0.235 g, 56%). Mp: 109-111 °C. 1H NMR
(CDCl3): δ 8.05 (m, 4H) and 7.68-7.35 (m, 7H), 6.13 (d, 3.1
Hz, 1H), 5.40 (dd, 8.2 Hz, 1H), 4.85-4.53 (m, 4H), 4.29 (m,
1H), 3.84 (m, 1H), 3.63 (m, 3H), 3.20 (m, 3H), 2.80 (m, 1H).
13C NMR (CDCl3): δ 166.5, 165.8, 163.5, 150.5, 139.0, 133.8,
133.3, 129.7, 129.6, 129.4, 129.1, 128.7, 128.5, 102.7, 86.1, 75.6,
68.4, 64.0, 61.8, 58.6, 52.5, 48.2. HRMS (CI, M + H+): for
C
27H28N3O9S calcd 570.1546, obsd 570.1577.
1-[5-O-Ben zoyl-2,3-d id eoxy-2-N-cycloh exyl-4H-2,3,5,6-
t et r a h yd r o-1,4-t h ia zin e-1,1-d ioxid es-â-D-r ibo-fu r a n osy-
l]u r a cil 12 (0.16 g, 58%). Mp: 125-127 °C. 1H NMR
(CDCl3): δ 8.86 (bs, 1H), 8.05-7.47 (m, 6H), 6.37 (d, 7.5 Hz,
1H), 5.60 (d, 8.1 Hz, 1H), 5.11 (m, 1H), 4.77 (m, 2H), 3.79 (m,
2H), 3.47 (m, 2H), 3.03 (m, 2H), 2.63 (m, 1H), 1.64 (m, 4H),
1.05 (m, 6H). 13C NMR (CDCl3): δ 165.9, 163.5, 150.5, 138.9,
133.9, 129.5, 129.1, 128.8, 102.9, 82.5, 73.0, 65.8, 64.2, 62.4,
58.9, 48.3, 44.7, 32.8, 31.4, 25.6, 25.4. HRMS (CI, M + H+):
for C24H30N3O7S calcd 504.1804, obsd 504.1796.
1-[5-O-Ben zoyl-2,3-d id eoxy-3-S-(2-N-b en zoyl-p -m et h -
oxya n ilin oet h ylsu lfon yl)-â-D-glycer op en t -2-en ofu r a n o-
syl]u r a cil 13 (0.19 g, 63%). Mp: 112-114 °C; 1H NMR
(CDCl3): δ 9.20 (bs, 1H), 7.99 (m, 2H), 7.60-6.70 (m, 15H),
5.57 (m, 1H), 5.18 (d, 8.1 Hz, 1H), 4.95 (2d, 1H), 4.65 (2d, 1H),
4.28 (m, 2H), 3.75 (s, 3H), 3.63 (m, 2H). 13C NMR (CDCl3): δ
171.0, 165.9, 163.3, 158.6, 150.6, 144.9, 139.9, 139.1, 135.0,
134.8, 133.6, 130.2, 129.5, 128.8, 127.9, 114.8, 103.2, 88.2, 82.7,
63.9, 55.4, 51.6, 44.7. HRMS (EI, M+): for C32H29N3O9S calcd
631.1625, obsd 631.1600.
1-[5-O-Tr ityl-3-d eoxy-3-S-(2-O-ter t-bu tyld im eth ylsilyl-
eth yl)-â-D-a r a -fu r a n osyl]u r a cil 19. To a solution of 3 (1 g,
1.8 mmol) and imidazole (0.27 g, 4 mmol) in DMF (10 mL)
was added tert-butyldimethylsilyl chloride (2.5 mmol) and the
reaction mixture was stirred at room temperature for 8 h. The
solution was then poured into ice-cold water and filtered. The
residue was dissolved in EtOAc, dried over Na2SO4, and
filtered. The filtrate was evaporated to dryness and the white
residue was purified over silica gel to give 19 (1.1 g, 93%).
Mp: 77-79 °C. 1H NMR (CDCl3): δ 9.50 (bs, 1H), 8.11 (d,
8.2 Hz, 1H), 7.46-7.27 (m, 15H), 6.16 (d, 5.2 Hz, 1H), 5.34 (d,
8.1 Hz, 1H), 4.72 (d, 1H), 4.55 (m, 1H), 3.83 (m, 3H), 3.50 (m,
3H), 2.79 (m, 2H), 0.88 (s, 9H), 0.06 (s, 6H). 13C NMR (CDCl3)
Gen er a l P r oced u r e for th e Syn th esis of 8-10.
A
mixture of 6 (0.271 g, 0.5 mmol) and the corresponding amine
(0.5 mmol) in MeOH (20 mL) was stirred at room temperature
for 22-72 h. MeOH was removed under reduced pressure.
The residue was purified over silica gel (8) or basic alumina
(9 and 10).
1-[5-O-Tr it yl-2,3-d id eoxy-2-N-isob u t yl-4H -2,3,5,6-t et -
r a h yd r o-1,4-t h ia zin e-1,1-d ioxid es-â-D-r ibo-fu r a n osyl]-
1
u r a cil 8 (0.25 g, 83%). Mp: 134-138 °C; H NMR (CDCl3):
δ 7.86 (d, 8.2 Hz, 1H), 7.37-7.27 (m, 15H), 6.31 (d, 6.1 Hz,
1H), 5.22 (d, 8.1 Hz, 1H), 4.80 (m, 1H), 3.81 (t, 1H), 3.64 (m,
4H), 3.10 (m, 3H), 2.73 (m, 1H), 2.28 (m, 1H), 1.65 (m, 1H),
0.87 (d, 6H). 13C NMR (CDCl3): δ 163.6, 150.6, 142.9, 139.6,
128.7, 128.3, 127.8, 102.6, 88.4, 83.3, 75.4, 69.2, 64.3, 62.5, 58.5,
47.7, 47.2, 27.3, 20.3, 20.2. HRMS (CI, M + H+) for
C
34H38N3O6S calcd 616.2481, obsd 616.2432.
1-[5-O-Tr ityl-2,3-dideoxy-2-N-ben zyl-4H-2,3,5,6-tetr ah y-
d r o-1,4-th ia zin e-1,1-d ioxid es-â-D-r ibo-fu r a n osyl]u r a cil 9
(0.27 g, 83%). Mp: 143-144 °C. 1H-1H COSY NMR
(CDCl3): δ 7.81 (d, 8.2 Hz, 1H) H-6; 7.43-7.22 (m, 20H)
aromatic, 6.31 (d, 4.5 Hz, 1H) H-1′; 5.13 (d, 8.2 Hz, 1H) H-5;
4.82 (m, 1H) H-4′; 4.30 (d, 14.4 Hz, 1H) one of benzyl CH2;
3.79-3.52 (m, 6H) H-3′, H-5′, H-5′′, SO2CH2 and one of benzyl
CH2; 3.20-3.09 (m, 3H) H-2′, NCH2. 13C NMR (CDCl3): δ
163.7, 150.6, 142.9, 139.5, 137.6, 128.9, 128.8, 128.3, 128.2,
127.9, 127.7, 102.6, 88.3, 84.4, 76.4, 68.7, 63.5, 58.4, 47.7.
HRMS (EI, M+) for C37H35N3O6S calcd 649.2247, obsd 649.2189.
(22) Compound 11 was synthesized in 0.73 mmol scale. Compounds
12 and 13 were prepared in 0.55 mmol scale. In the preparation of 13,
the suspension of 7 and p-methoxyaniline in MeOH was stirred at room
temperature followed by heating under reflux for 10 h to initiate
cyclization.

Sugar-Modified Uridine Bisvinyl Sulfone
J . Org. Chem., Vol. 63, No. 6, 1998 1759
δ 164.8, 151.4, 143.5, 142.4, 128.9, 128.2, 127.5, 101.4, 87.5,
85.6, 81.7, 78.1, 63.3, 62.4, 48.3, 34.2, 26.1, 18.5, -5.0. HRMS
(EI, M+): for C36H44N2O6SSi calcd 660.2690, obsd 660.2648.
1-[5-O-Tr ityl-2,3-d id eoxy-3-S-(2-O-ter t-bu tyld im eth yl-
silyle t h ylsu lfon yl)-â-D -glyce r op e n t -2-e n ofu r a n osyl]-
u r a cil 21. Compound 19 (0.9 g, 1.36 mmol) was oxidized with
MMPP (2.5 g, 5.5 mmol) in MeOH (25 mL) following the same
method as described for 5 to give 20 (0.85 g, 90%). To a
solution of compound 20 (0.8 g, 1.18 mmol) in pyridine (10 mL)
was added mesyl chloride (0.3 mL, 3.6 mmol) dropwise at 0
°C. After the addition the reaction mixture was kept at 4 °C
overnight. Water (2 mL) was added to the reaction mixture.
The mixture was then heated at 40 °C for 1.5 h. The mixture
cooled to room temperature and was poured into saturated
NaHCO3 solution. The residue was filtered, washed with
water, and then dissolved in EtOAc. The EtOAc part was
dried over Na2SO4 and filtered. The filtrate was evaporated
to dryness under reduced pressure and the residue was
purified over silica gel to give 21 (0.67 g, 86%). Mp: 87-90
°C. 1H NMR (CDCl3): δ 7.90 (d, 8.0 Hz, 1H), 7.41-7.27 (m,
15H), 7.09 (m, 1H), 6.78 (t, 1H), 5.20 (m, 1H), 4.79 (d, 8.1 Hz,
1H), 4.02 (t, 2H), 3.75 (m, 2H), 3.30 (m, 2H), 0.92 (s, 9H), 0.10
(s, 6H). 13C NMR (CDCl3): δ 163.3, 150.6, 147.8, 142.8, 140.8,
137.3, 129.1, 128.6, 127.6, 102.9, 88.4, 87.7, 84.4, 63.1, 58.4,
56.9, 25.9, 18.3, -5.4. HRMS (CI, M + H+): for C36H43N2O7-
SSi calcd 675.2560, obsd 675.2608.
1-[5-O-Tr it yl-2,3-d id eoxy-2-N-b en zyla m in o-3-S-(2-O-
ter t-bu tyld im eth ylsilyleth ylsu lfon yl)-â-D-xylo-fu r a n osy-
l]u r a cil 22. Compound 21 (0.52 g, 0.77 mmol) was treated
with benzylamine (1.3 g, 12 mmol) in dichloromethane (20 mL)
for 3 days. Dichloromethane was removed under reduced
pressure and the gummy residue was triturated with petro-
leum ether. The white residue was purified over silica gel to
give 22 (0.48 g, 79%). Mp: 92-94 °C. 1H NMR (CDCl3): δ
7.58 (d, 8.2 Hz, 1H), 7.51-7.22 (m, 20H), 5.94 (d, 4.4 Hz, 1H),
5.62 (d, 8.2 Hz, 1H), 4.61 (m, 1H), 3.94-3.63 (m, 9H), 3.02 (m,
2H), 0.90 (s, 9H), 0.05 (2s, 6H). 13C NMR (CDCl3): δ 163.5,
150.9, 143.5, 140.4, 138.8, 128.9, 128.2, 128.1, 127.6, 127.4,
102.9, 89.1, 87.9, 78.1, 69.2, 64.5, 62.6, 57.7, 56.4, 51.5, 26.0,
18.4, -5.4. HRMS (CI, M + H+): C43H52N3O7SSi calcd
782.3295, obsd 782.3276.
Hz, 1H), 3.86 (d, 11.4 Hz, 1H), 3.67 (m, 1H), 3.52 (d, 11.4 Hz,
1H), 2.74 (m, 2H). 13C NMR (CDCl3): δ 166.2, 163.9, 150.4,
142.7, 139.5, 133.4, 129.6, 128.8, 128.5, 128.3, 127.6, 102.1,
89.6, 87.7, 84.2, 69.6, 63.9, 59.9, 45.7, 31.0. HRMS (CI, M +
H+): for C37H34N5O6S calcd 676.2230, obsd 676.2239.
1-[5-O-Tr ityl-2,3-d id eoxy-2-a zid o-3-S-(2-h yd r oxyeth yl)-
â-D-r ibo-fu r a n osyl]u r a cil 25. To a solution of 24 (1.25 g,
1.84 mmol) in ethanol (50 mL) and water (10 mL) was added
1 N NaOH solution (10 mL) and the reaction mixture was
stirred at room temperature for 2 h. The mixture was then
neutralized with 1 N HCl. Saturated NaHCO3 solution was
added to the mixture followed by water (100 mL). The
precipitate was filtered, washed with water, and air-dried. The
residue was dissolved in EtOAc, dried over anhydrous Na2-
SO4, and filtered. The filtrate was evaporated to dryness and
the residue was purified over silica gel to give 25 (1 g, 95%).
Mp: 87-88 °C. IR: 2140 cm-1 1H NMR (CDCl3): δ 9.54 (bs,
.
1H), 8.17 (d, 8.1 Hz, 1H), 7.44-7.27 (m, 15H), 5.87 (s, 1H),
5.28 (d, 8.1 Hz, 1H), 4.49 (d, 5.1 Hz, 1H), 4.05 (d, 10.0 Hz,
1H), 3.80 (m, 4H), 3.54 (d, 1H), 2.64 (t, 2H), 2.45 (bs, 1H). 13C
NMR (CDCl3): δ 164.1, 150.7, 143.1, 140.1, 128.8, 128.1, 127.6,
101.9, 89.7, 87.6, 83.9, 69.5, 62.6, 60.4, 46.0, 35.1. HRMS (CI,
M + H+): for C30H30N5O5S calcd 572.1968, obsd 572.1925.
1-[5-O-Tr ityl-2,3-d id eoxy-2-a zid o-3-S-(2-h yd r oxyeth yl-
su lfon yl)-â-D-r ibo-fu r a n osyl]u r a cil 26. Compound 25 (0.86
g, 1.5 mmol) was oxidized with MMPP (2.8 g, 5.6 mmol) in
MeOH (30 mL) following the same method as described for 5
to give 26 (0.79 g, 87%). Mp: 110-112 °C. IR: 2125 cm-1
.
1H NMR (CDCl3): δ 9.54 (bs, 1H), 8.05 (d, 8.3 Hz, 1H), 7.50-
7.20 (m, 15H), 5.94 (d, 0.8 Hz, 1H), 5.31 (d, 8.1 Hz, 1H), 4.79
(m, 2H), 4.47 (m, 1H), 3.96 (m, 3H), 3.56 (d, 1H), 2.97 (m, 2H).
13C NMR (CDCl3): δ 163.5, 150.2, 142.4, 139.1, 128.5, 127.8,
127.3, 102.1, 88.5, 87.6, 65.7, 61.6, 61.1, 56.9, 55.6. HRMS
(EI, M+): for C30H29N5O7S calcd 603.1788, obsd 603.1772.
1-[5-O-Tr ityl-2,3-d id eoxy-2-N-4H-2,3,5,6-tetr a h yd r o-1,4-
th ia zin e-1,1-d ioxid es-â-D-r ibo-fu r a n osyl]u r a cil 28. Com-
pound 26 (0.5 g, 0.82 mmol) was dissolved in EtOAc (7 mL)
and Pd/C (10% Pd, 0.08 g) was added. The reaction mixture
was then shaken under hydrogen pressure of 30 lbs/in. for 4
h. Pd/C was filtered off and the filtrate was evaporated to
dryness to produce 27. To a solution of the crude product 27
and Ph3P (0.24 g, 0.9 mmol) in dichloromethane (20 mL) was
added diisopropyl azadicarboxylate (0.2 mL, 1 mmol) dropwise
at 0 °C. After the addition, the reaction mixture was stirred
at room temperature for 2 h. The organic solvent was removed
under reduced pressure and the gummy residue was purified
over silica gel column to give 28 (0.34 g, 74%). Mp: 162-165
°C. 1H NMR (CDCl3): δ 9.46 (bs, 1H), 8.15 (d, 8.2 Hz, 1H),
7.46-7.25 (m, 15H), 5.66 (s, 1H), 5.11 (d, 8.1 Hz, 1H), 4.75 (d,
10.2 Hz, 1H), 3.91 (m, 3H), 3.62 (d, 10.2 Hz, 1H), 3.40-3.06
(m, 5H). 13C NMR (CDCl3): δ 163.7, 150.8, 142.9, 139.8, 128.7,
128.1, 127.5, 101.9, 89.3, 88.0, 79.2, 64.9, 61.5, 59.3, 50.9, 42.6.
HRMS (CI, M + H+) for C30H30N3O6S calcd 560.1855, obsd
560.1830.
1-[5-O-Tr it yl-2,3-d id eoxy-2-N-b en zyla m in o-3-S-(2-h y-
d r oxyeth ylsu lfon yl)-â-D-xylo-fu r a n osyl]u r a cil 23. Com-
pound 22 (0.35 g, 0.44 mmol) was treated with tetrabutylam-
monium fluoride (0.18 g, 0.68 mmol) in dioxane (10 mL) for
0.5 h. The reaction mixture was then poured into ice cold
water (50 mL) and extracted with dichloromethane (2 × 20
mL). The combined dichloromethane part was dried over
anhydrous Na2SO4 and filtered. The gummy residue was
purified over silica gel to produce 23 (0.25 g, 90%). Mp: 125-
126 °C. 1H NMR (CDCl3): δ 7.56 (d, 8.1 Hz, 1H), 7.46-7.28
(m, 20H), 5.97 (d, 4.3 Hz, 1H), 5.63 (d, 8.1 Hz, 1H), 4.60 (m,
1H), 3.97-3.64 (m, 8H), 3.05 (m, 2H). 13C NMR (CDCl3): δ
163.8, 150.9, 143.6, 143.3, 140.6, 138.6, 128.7, 128.3, 128.0,
127.4, 103.1, 88.6, 87.8, 77.5, 68.1, 63.9, 62.2, 56.2, 51.1.
HRMS (EI, M+): for C37H37N3O7S calcd 667.2352, obsd 667.2341.
Attem p ted Cycliza tion of 23. To a solution of 23 (0.3 g,
0.45 mmol) and Ph3P (0.15 g, 0.57 mmol) in dichloromethane
(20 mL) was added diisopropyl azadicarboxylate (0.14 mL, 0.7
mmol) dropwise at 0 °C. After the completion of addition, the
reaction mixture was stirred at room temperature for 6 h. The
reaction mixture afforded a complex mixture of products (TLC).
1-[5-O-Tr ityl-2,3-dideoxy-2-azido-3-S-(2-O-ben zoyleth yl)-
â-D-r ibo-fu r a n osyl]u r a cil 24. To a solution of 4 (2 g, 3.15
mmol) in DMF (30 mL) was added LiN3 (2 g, 40 mmol) and
the reaction mixture was heated at 140 °C for 3 h. The
mixture was cooled to room temperature and poured into
saturated NaHCO3 solution. The white precipitate was fil-
tered, washed with water, dried, and dissolved in EtOAc. The
EtOAc part was dried over anhydrous Na2SO4 and filtered.
The filtrate was evaporated to dryness and the residue was
purified over silica gel to give 24 (1.5 g, 70%). Mp: 81-83 °C.
1-[5-O-Tr it yl-2,3-d id eoxy-2-N-b en zyla m in o-3-S-(2-h y-
d r oxyeth ylsu lfon yl)-â-D-r ibo-fu r a n osyl]u r a cil 29. Com-
pound 26 (0.33 g, 0.55 mmol) was reduced to compound 27
following the same method as described above. To a solution
of crude 27 in EtOH (50 mL) were added water (6 mL) and
acetate buffer (1.4 mL) [prepared from NaOAc‚3H2O (2.5 g),
glacial HOAc (8.4 mL), and water (25 mL)] followed by the
addition of benzaldehyde (0.15 g, 1.4 mmol). The reaction
mixture was stirred at 0-5 °C for 0.5 h and then NaBH4 (0.15
g, 5 mmol) was added portionwise over a period of 1 h. The
solvent was removed under reduced pressure. To the residue
was added water (25 mL) and the mixture was extracted with
chloroform (3 × 20 mL). The combined organic extracts were
washed with water (25 mL), dried over Na2SO4, and filtered,
and the filtrate was evaporated under reduced pressure. The
product was purified over silica gel to give 29 (0.15 g, 40%).
Mp: 77-79 °C. 1H NMR (CDCl3): δ 8.86 (bs, 1H), 7.67 (d,
8.0 Hz, 1H), 7.30 (m, 20H), 6.14 (d, 6.5 Hz, 1H), 5.30 (d, 8.2
Hz, 1H), 4.86 (m, 1H), 4.10-3.25 (m, 10H). 13C NMR (CDCl3
+ DMSO-d6): δ 163.3, 151.0, 143.5, 140.1, 139.6, 128.7, 128.3,
128.1, 127.5, 127.2, 102.3, 87.5, 87.4, 75.7, 64.9, 63.1, 62.9, 56.5,
IR: 2130 cm-1 1H NMR (CDCl3): δ 9.10 (bs, 1H), 8.19 (d, 8.2
.
Hz, 1H), 7.99 (m, 2H) and 7.64-7.27 (m, 18H), 5.91 (s, 1H),
5.25 (d, 8.2 Hz, 1H), 4.44 (m, 1H), 4.30 (m, 2H), 4.08 (d, 10.8

1760 J . Org. Chem., Vol. 63, No. 6, 1998
Bera et al.
55.5, 51.5. HRMS (EI, M+) for C37H37N3O7S calcd 667.2352,
obsd 667.2332.
0.5% aqueous NaCN solution (50 mL). The aqueous part was
washed with chloroform (2 × 10 mL). The combined chloro-
form part was then washed thoroughly with water, dried over
Na2SO4, and evaporated to dryness. The residue was purified
over silica gel to yield 10 (0.1 g, 87%).
Com p ou n d 28 fr om Com p ou n d 9. To a solution of 9 (0.42
g, 0.64 mmol) in 4% formic acid in methanol (25 mL) was added
Pd/C (0.3 g, 10% Pd) and the solution was heated at 80 °C for
10 min. The suspension was filtered. Excess aqueous NH3
solution was added to the filtrate and the solution was
evaporated to dryness. The residue was partitioned between
EtOAc and water. The EtOAc part was dried over Na2SO4
and evaporated to dryness. The solid residue was purified over
silica gel to give compound 28 (0.27 g, 75%).
Com p ou n d 10 fr om Com p ou n d 28. To a solution of 28
(0.11 g, 0.19 mmol) and allyl bromide (0.05 g, 0.41 mmol) in
DMF (2 mL) was added Ag2O (0.06 g) and the reaction mixture
was stirred at room temperature for 1.25 h. After allowing
the precipitate to settle, DMF solution was slowly decanted
off. The precipitate was washed with chloroform (3 × 5 mL).
The combined organic part (DMF and CHCl3) was washed with
Ack n ow led gm en t. S.B. thanks UGC, New Delhi,
India, for a fellowship.
Su p p or tin g In for m a tion Ava ila ble: Copies of both 1H
and 13C NMR spectra of 3, 5, 6, 9, 10, 14, 15, and 28 and copies
of 1H NMR of 4, 8, 11, 12, 15, 19, 21, 22, 23, 24, 25, 26 and 29
(31 pages). This material is contained in libraries on micro-
fiche, immediately follows this article in this microfilm version
of the journal, and can be ordered from the ACS; see any
current masthead page for ordering information.
J O9705576