Novel chalcogenides of thymidine and uridine: synthesis, properties and applications

Article abstract of DOI:10.1016/j.carres.2007.02.035

A facile and efficient methodology has been developed for the synthesis of dithymidine and di-uridine derived disulfides using benzyltriethylammonium tetrathiomolybdate as a sulfur transfer reagent. However, a similar reaction of thymidine derivative with tetraethylammonium tetraselenotungstate as a selenium transfer reagent resulted in the formation of an unexpected cyclic diselenide. The disulfide derivatives of nucleosides have been used as precursors in a tandem disulfide cleavage-Michael addition/ring opening reactions to construct aminoacid and carbocyclic derivatives of nucleosides.

Full text of DOI:10.1016/j.carres.2007.02.035

Carbohydrate Research 342 (2007) 1151–1158
Novel chalcogenides of thymidine and uridine: synthesis,
properties and applications
Kirubakaran Sivapriya, Perumal Suguna, S. Shubashree, Perali Ramu Sridhar
and Srinivasan Chandrasekaran*
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
Received 1 November 2006; received in revised form 19 February 2007; accepted 10 March 2007
Available online 4 March 2007
Abstract—A facile and efficient methodology has been developed for the synthesis of dithymidine and di-uridine derived disulfides
using benzyltriethylammonium tetrathiomolybdate as a sulfur transfer reagent. However, a similar reaction of thymidine derivative
with tetraethylammonium tetraselenotungstate as a selenium transfer reagent resulted in the formation of an unexpected cyclic disel-
enide. The disulfide derivatives of nucleosides have been used as precursors in a tandem disulfide cleavage-Michael addition/ring
opening reactions to construct aminoacid and carbocyclic derivatives of nucleosides.
ꢀ 2007 Elsevier Ltd. All rights reserved.
Keywords: Nucleosides; Tetrathiomolybdate; Tetraselenotungstate; X-ray crystallography
1. Introduction
considerable interest in the synthesis of thionucleoside
analogues5a–g (Chart 1).
In the past few years modified nucleosides especially
thio- and seleno-substituted nucleosides have gained
much attention. This is because the sulfur or selenium
functionalities present in sugar precursors play a pivotal
role in directing b-selective coupling reactions with
bases. These functionalities can be removed easily either
thermally or reductively to produce dideoxynucleo-
sides.1 Many modified deoxynucleosides have been
shown to exhibit antiretroviral and anticancer activities
of varying potency.2 Selenols derived from deoxynucleo-
sides are known for their susceptibility to oxidation.
Nucleoside analogues like 30-azido-30-deoxythymidine
(AZT) and 20-fluoro-50-thio analogues have been dem-
onstrated to have anti-HIV and antitumor activity.3
The important role of S-adenosyl-L-methionine (SAM)
in biological methylation reactions4a–c has attracted
The chemical stability of the 50-bridging sulfur atom
makes it a good candidate for use as a physical and
mechanistic probe for specific protein or metal interac-
tions involving this position in DNA6a and heavy metal
labelled 50-thiooligonucleotides are interesting sub-
strates in the study of DNA-binding proteins by
X-ray crystallography.6b The 50-disulfide derivatives
and other 50-thionucleosides were mainly synthesized
involving the use of their respective thiols produced
in situ7a,b and the diselenide derivatives from selenols
and selenocyanides.8
In this paper we report a facile and efficient route to
the synthesis of 50-thio and 50-seleno derivatives of
thymidine and uridine. The synthesis of disulfides of
thymidine and uridine has been accomplished using
our efficient sulfur transfer reagent, benzyltriethylam-
monium tetrathiomolybdate, [BnEt3N]2MoS4 1.9 The
disulfides derived from thymidine and uridine have been
effectively used in tandem disulfide cleavage-Michael
addition/ring opening reactions to form amino acid
and carbocyclic derivatives of nucleosides. Interest-
ingly, the selenium transfer reaction of thymidine with
*
Corresponding author. Address: Jawaharlal Nehru Centre for
Advanced Scientific Research, Jakkur, Bangalore, India. Tel.: +91
80 2293 2404; fax: +91 80 2360 2423; e-mail: scn@orgchem.
iisc.ernet.in
0008-6215/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2007.02.035

1152
K. Sivapriya et al. / Carbohydrate Research 342 (2007) 1151–1158
NH2
O
N
N
N
H3C
N
CH3
S
NH
HOOC
N
O
HO
O
O
NH2
OH
OH
N3
AZT
SAM
Chart 1.
tetraselenotungstate, [Et4N]2WSe4 210 led to the forma-
tion of an unexpected cyclic diselenide 9.
(1.1 equiv, MeCN, 28 ꢁC, 18–20 h) gave the correspond-
ing disulfides 5 and 8, respectively, in good yields (77–
82%). Attempts at the introduction of sulfur at the 20
and/or 30-positions of the nucleosides (adenosine, gua-
nosine and thymidine) using the present methodology
were not satisfactory and the starting materials were
recovered unchanged.
Thymidine derived disulfide 8 was found to be a crys-
talline solid and its molecular structure was confirmed
by X-ray crystallography (Fig. 1).
2. Results and discussion
2.1. Synthesis of thymidine and uridine derived disulfides
The formation of uridine and thymidine derived disul-
fides 5 and 8 from their respective bases in good yields
is depicted in Scheme 1. Uridine 3 was protected as its
acetal using standard procedure, which on treatment
with p-toluenesulfonyl chloride in pyridine furnished
the tosylate 4 in 92% yield.11 Similarly, 5-O-tosyl-3-O-
acetyl thymidine 7 was synthesized (90%) from thymi-
dine 6 by tosylation12 (p-TsCl/Py, ꢀ10 ꢁC, 8 h) followed
by acetylation (Ac2O, 0 ꢁC, 3 h) in one pot. The tosyl-
ates 4 and 7 when treated with tetrathiomolybdate 1
2.2. Synthesis of thymidine and uridine derived diselenides
When thymidine derived tosylate 7 was treated with tetra-
selenotungstate 2 (1.1 equiv, MeCN, 28 ꢁC, 22 h) an
unexpected cyclic diselenide 9 with an inverted configu-
ration at C-3 was obtained in good yield (82%) (Scheme
2). Compound 9 showed two peaks (d 301 for Se1 and d
O
O
O
N
NH
NH
NH
HO
TsO
N
O
S
N
O
O
2
O
O
C
O
C
c
a, b
OH
OH
O
O
O
O
Me2
Me2
5
4
3
a. 2,2'-Dimethoxypropane,
TsOH, DMF, 90%
c. (BnEt3N)2MoS4 1, MeCN,
b.
p
-TsCl/Py, -10 ºC, 92%
rt, 20 h, 77%
O
O
O
H3C
NH
H3C
NH
H3C
NH
N
O
HO
N
O
TsO
N
O
S
O
O
2
c
a, b
O
OH
H
OAC
H
OAC
H
6
7
8
c. (BnEt3N)2MoS4 1, MeCN,
b. Ac2O, 0 ºC, 90%
a. p-TsCl/Py, -10 ºC, 94%
rt, 18 h, 82%
Scheme 1.

K. Sivapriya et al. / Carbohydrate Research 342 (2007) 1151–1158
1153
O
N
H3C
NH
(Et4N)2WSe4
MeCN, rt, 22 h
2
O
1Se
2Se
O
7
82%
9
O
NH
(Et4N)2WSe4
MeCN, rt, 20 h
2
N
O
Se
4
2
O
74%
O
O
C
Me2
10
Scheme 2.
Figure 1. ORTEP diagram of 8 (the other half of the molecule was not
and the presence of cyclic diselenide was not detected
(Scheme 2). The 77Se NMR of compound 10 shows a
single peak at d 291 as expected.
labelled for clarity).
502 for Se2) in the 77Se NMR spectrum. The molecular
structure of 9 was confirmed by single crystal X-ray
analysis (Fig. 2). Similar cyclic diselenides were reported
previously but the synthesis involved longer routes giv-
ing lower yields.13 The neighbouring group participation
reaction to end up with an inverted configuration at C-3
has been reported earlier in the synthesis of 30-azido-
20,30-dideoxyadenosine.14 Interestingly, when uridine
derived tosylate 4 was treated with tetraselenotungstate
2 (1.1 equiv, MeCN, 28 ꢁC, 20 h) the corresponding uri-
dine derived diselenide 108 was obtained in 74% yield
To study the role of the base in the formation of the
cyclic diselenide like 9, a simple 2-deoxy sugar 11 was
used as the substrate. The tosylate 12 was synthesized
in 91% yield in one pot by stirring the deoxy sugar
1115 with p-TsCl/Py at ꢀ10 ꢁC for 5 h followed by the
addition of Ac2O (0 ꢁC, 2 h) (Scheme 3). Treatment of
12 with tetraselenotungstate 2 (1.1 equiv, MeCN,
28 ꢁC, 10 h) afforded the cyclic diselenide 13 (88%). As
expected 13 exhibited two peaks (d 290 for Se1 and d
430 for Se2) in the 77Se NMR spectrum. The structure
Figure 2. ORTEP diagram of 9 (hydrogens are not shown for clarity) and 13.
TsO
a
HO
O
1Se
O
O
b
2Se
OCH3
OCH3
OCH3
OAC
OH
11
13
b. (Et4N)2WSe4 2, MeCN, rt, 10 h, 88%
12
ii. Ac2O, 0 °C
a. i. p-TsCl/ Py, -10 °C, 99%
Scheme 3.

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K. Sivapriya et al. / Carbohydrate Research 342 (2007) 1151–1158
of the product of 13 was further confirmed by X-ray
crystallography (Fig. 2).
2.4. Application of disulfides 5 and 8 in the modification
of nucleosides
2.3. Proposed mechanism for the formation of cyclic
diselenide 13
The next step was the application of disulfides 5 and 8 in
the modification of nucleosides. Accordingly thymidine
derived disulfide 8 was allowed to react with tetrathio-
molybdate 1 in the presence of epoxide 14 (MeCN,
6 h, 28 ꢁC). The b-hydroxy sulfide derivative 15 was iso-
lated as a 1:1 mixture of diastereomers in reasonable
yield (64%). In this reaction in the first step tetrathio-
molybdate 1 cleaves the disulfide bond17 to give the
corresponding thiolate in situ, which immediately opens
the epoxide 14 to give the product 15. Similarly, when
the reaction of 8 was carried out with 1 in the presence
of a Michael acceptor like 16 (MeCN, 6 h, 28 ꢁC) the
nucleoside derived amino acid 17 was obtained in 61%
yield and it was found to be racemic (Scheme 5). The
sulfides similar to 17 were previously prepared from
The proposed mechanism for the formation of the disel-
enide 13 is shown in Scheme 4. The first step is the nucleo-
phillic attack of tetraselenotungstate 2 on tosylate 12,
which will give the alkylated intermediate 12a. The inter-
mediate 12a on intramolecular displacement of acetate
by selenium followed by the diselenide formation in an
internal redox process16a–d furnishes the cyclic diselenide
13. However, it should be pointed that the reaction of
30,50-ditosyl derivatives of thymidine 6 and 2-deoxy sugar
11 with tetraselenotungstate 2 (1.1 equiv, MeCN, 28 ꢁC)
gave a mixture of products along with the cyclic disele-
nides 9 and 13, respectively, which were difficult to purify.
TsO
Se
Se
Se
Se
Se
Se
Se
Se
O
(Et4N)2WSe4
OCH3
2
Se
Se
O
O
W
W
O
WSe2
OCH3
OCH3
OCH3
OAc
OAc
13
12a
12
Scheme 4.
OH
MeCN, 6 h, 64%
14,
S
B
O
OAc
B
S
O
NHAc
(BnNEt3N)MoS4 1
15
O
8
S
OAc
MeOOC
MeCN, 6 h, 61%
B
NH
B=
O
H
16,
N
O
OAc
17
NHTs
S
O
B
S
B
O
C
(BnNEt3N)MoS4 1
NH
O
C
MeCN, 6 h, 72%
18,
B=
5
N
O
O
O
O
O
Me2
Me2
19
MeOOC
NHAc
O
NTs
16
14
18
Scheme 5.

K. Sivapriya et al. / Carbohydrate Research 342 (2007) 1151–1158
1155
the 50-tosyl intermediates through reactions with the
Table 1. C–Hꢁ ꢁ ꢁO and N–Hꢁ ꢁ ꢁO intermolecular interactions of 8
corresponding thiols.5c But the 50-tosyl intermediates
were found to be not very stable and generally gave a
lower yield of the sulfides.18
D–Hꢁ ꢁ ꢁA
Distance
Distance
Angle
˚
˚
Hꢁ ꢁ ꢁA (A) Dꢁ ꢁ ꢁA (A) D–Hꢁ ꢁ ꢁA (ꢁ)
C(4)–H(4)ꢁ ꢁ ꢁO(5)i
2.58(5)
3.418(7)
3.185(6)
3.347(5)
2.849(6)
153(4)
135(7)
159(4)
176(5)
C(12)–H(12A)ꢁ ꢁ ꢁO(4)ii 2.49(8)
Treatment of uridine derived disulfide 5 with tetra-
thiomolybdate 1 (1.1 equiv, MeCN, 3 h) in the presence
of aziridine 18 (1.2 equiv, 28 ꢁC, 6 h) resulted in the for-
mation of b-amino sulfide derivative 19 in 72% yield
(Scheme 5). By the use of these reactions a nucleoside
can be attached through a 50-sulfide linkage to a carbo-
cycle or an amino acid by choosing the right donor and
acceptor.
C(2)–H(2B)ꢁ ꢁ ꢁO(1)iii
2.21(5)
2.00(5)
N(2)–H(2)ꢁ ꢁ ꢁO(3)iv
Symmetry codes: (i) 1/2 + x, ꢀ1/2 + y, z, (ii) 1/2 ꢀ x, 1/2 + y, ꢀz, (iii)
x, 1 + y, z, (iv) ꢀ1/2 + x, ꢀ1/2 + y, z.
2.5. Structural studies
Molecular packing of disulfide 8 shows strong NHꢁ ꢁ ꢁO
and CHꢁ ꢁ ꢁO interactions (Fig. 3). The distances and
the angles are given in Table 1. There is only one strong
NHꢁ ꢁ ꢁO hydrogen bonding with a distance (Dꢁ ꢁ ꢁH)
˚
2.00 A. But this NHꢁ ꢁ ꢁO hydrogen bonding is not simi-
lar to the base pair interaction, which is commonly
found in nucleosides. The oxygen of the carbonyl of 2-
acetyl group participates in this strong interaction rather
than the pyrimidine carbonyl group. It is apparent that
the CHꢁ ꢁ ꢁO interactions overcome the NHꢁ ꢁ ꢁO interac-
tions. There are three strong CHꢁ ꢁ ꢁO interactions that
are found in this molecule (Table 1).
However, the molecular packing of cyclic diselenide 9
shows a dimeric packing pattern, which is found in all
nucleoside bases (Fig. 4).19 The packing is due to strong
NHꢁ ꢁ ꢁO and CHꢁ ꢁ ꢁO interactions. The NH of one base
interacts with the carbonyl of the adjacent base. This
Figure 4. Packing diagram of 9 indicating C–Hꢁ ꢁ ꢁO and N–Hꢁ ꢁ ꢁO
˚
strong NHꢁ ꢁ ꢁO interaction with a distance of 2.34 A
interactions.
allows the molecule to pack in a dimeric fashion. Apart
from NHꢁ ꢁ ꢁO interaction, the carbonyl of the base inter-
acts with the hydrogen (H-3) of the deoxysugar moiety.
The distances and the angles are given in Table 2.
In conclusion, we provide an efficient and simple meth-
od to synthesize disulfides and diselenides of thymidine
and uridine derivatives. The molecular structures and
Figure 3. Packing diagram of 8 indicating C–Hꢁ ꢁ ꢁO and N–Hꢁ ꢁ ꢁO interactions.

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K. Sivapriya et al. / Carbohydrate Research 342 (2007) 1151–1158
Table 2. Intermolecular hydrogen bonding geometry and interactions
of 9
J2 = 7.8 Hz), 5.56 (d, 1H, J = 1.2 Hz), 5.09 (dd, 1H,
J1 = 1.5 Hz, J2 = 6.6 Hz), 4.85 (dd, 1H, J1 = 3.9 Hz,
J2 = 6.3 Hz), 4.38 (dd, 1H, J1 = 6.6 Hz, J2 = 10.5 Hz),
3.14–3.05 (m, 2H), 1.57 (s, 3H), 1.35 (s, 3H); 13C
NMR (75 MHz, CDCl3): d 163.7, 150.0, 143.2, 114.5,
102.7, 95.8, 86.5, 84.5, 83.3, 41.5, 27.1, 25.2; HRESIMS
(m/z): calcd for C24H30O10N2S2 (M+Na+): 621.1301,
obsd (M+Na+): 621.1248.
D–Hꢁ ꢁ ꢁA
Distance
Hꢁ ꢁ ꢁA (A)
2.34(5)
2.45(5)
Distance
Dꢁ ꢁ ꢁA (A)
2.954(8)
3.207(9)
Angle
D–Hꢁ ꢁ ꢁA (ꢁ)
172(7)
135(4)
˚
˚
N(2)–H(10)ꢁ ꢁ ꢁO(3)i
C(3)–H(3)ꢁ ꢁ ꢁO(3)ii
Symmetry codes: (i) ꢀ1/2 + x, ꢀ1/2 ꢀ y, ꢀz; (ii) 1/2 ꢀ x, ꢀy, 1/2 + z.
the interaction patterns of the new cyclic diselenide and
thymidine disulfide derivatives were studied by X-ray
crystallography. The utility of these disulfides in various
ring opening reactions as well in Michael addition reac-
tions has been demonstrated. By these simple and effi-
cient reactions a nucleoside can be attached to an
amino acid or a carbocyclic system effectively through a
sulfur linkage.
3.2.2. Bis-(30-O-acetyl-50-deoxy-50-thiothymidine)-5,50-
disulfide (8). Starting from 7 (0.1 g, 0.23 mmol); white
crystalline needles (crystallized from MeOH, 0.11 g,
25
82%); mp 83 ꢁC; ½aꢂD ꢀ24 (c 1, MeOH); 1H NMR
(300 MHz, CD3COCD3): d 7.49 (s, 1H), 6.27 (dd, 1H,
J1 = 6.0 Hz, J2 = 7.5 Hz), 5.24 (br t, 1H, J1 = 2.7 Hz,
J2 = 6 Hz), 4.36–4.20 (m, 3H), 2.45–2.32 (m, 2H), 2.07
(s, 3H), 2.04 (s, 3H); 13C NMR (75 MHz, CD3COCD3):
d 170.8, 164.3, 151.3, 136.2, 111.2, 85.4, 82.8, 75.0, 64.6,
37.2, 20.8, 12.5; HRESIMS (m/z): calcd for
C24H24O10N2S2 (M+Na+): 621.1301, obsd (M+Na+):
621.1341.
3. Experimental
3.1. General methods
Melting points reported are recorded in Buchi B540
¨
1
melting point apparatus and are uncorrected. H and
3.3. General procedure for the synthesis of diselenides 9,
10 and 13
13C NMR spectra were recorded on a JEOL—300 and
75 MHz spectrometer, respectively. Chemical shifts are
reported in parts per million downfield from the internal
reference, tetramethylsilane. Coupling constants are
reported wherever it is necessary in Hertz (Hz). Flash
column chromatography was performed on (230–400
mesh) silica gel. Mass spectra were recorded on a Q-
TOF electrospray instrument. [a]D values were recorded
in a JASCO P-1020 polarimeter. X-ray data collections
were recorded on a BRUKER-SMART APEX CCD-
Single Crystal Diffractometer.
To a stirred soln of the tosylates 4, 7 or 12 in MeCN
(2 ml), tetraethylammonium tetraselenotungstate
2
(0.12 g, 0.15 mmol) was added and the reaction mixture
was stirred for 22 h at 28 ꢁC. After the disappearance of
the starting material (TLC), the solvent was removed
under diminished pressure and the black residue was
extracted with MeOH–CH2Cl2 (1:9, 5 · 20 ml) and
filtered through a Celite pad. The filtrate was concen-
trated and the crude products were purified by flash
column chromatography on silica gel (230–400 mesh,
elution with MeOH–CHCl3 1:9) to furnish diselenides
10, 9 or 13, respectively.
3.2. General procedure for the synthesis of disulfides 5 and
8
To a stirred soln of the tosylates 411 or 712 (0.1 g,
0.23 mmol) in MeCN (3 ml), benzyltriethylammonium
tetrathiomolybdate 1 (0.15 g, 0.25 mmol) was added
and the reaction mixture was stirred for 18 h at 28 ꢁC.
After the disappearance of the starting material (TLC),
the solvent was removed under diminished pressure and
the black residue was extracted with MeOH–CH2Cl2
(1:9, 5 · 20 ml) and filtered through a Celite pad. The fil-
trate was concentrated and the crude products were
purified by flash column chromatography on silica gel
(230–400 mesh, elution with 1:9 MeOH–CHCl3) to
furnish compounds 5 or 8.
3.3.1. 1-(20,30,50-Trideoxy-30,50-diseleno-b-D-threo-pento-
furanosyl)thymine (9). Starting from
7
(0.06 g,
0.14 mmol); wine red crystalline solid (crystallized from
MeOH, 0.034 g, 0.09 mmol, 82%); mp: 204 ꢁC; ½aꢂ2D5 56 (c
1, CHCl3), 1H NMR (400 MHz, CDCl3): d 8.30 (s, 1H),
7.61 (s,1H), 6.08 (dd, 1H, J1 = 5.99 Hz, J2 = 8.3 Hz),
5.26 (br t, 1H, J = 5.8 Hz), 4.33 (dd, 1H, J1 = 7.6 Hz,
J2 = 15.4 Hz), 3.92 (d, 1H , J = 12.4 Hz) 3.37 (dd, 1H,
J1 = 3.5 Hz, J2 = 12.3 Hz), 3.05–2.98 (m, 1H), 2.29–
2.19 (m, 1H), 1.95 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 189.7, 163.3, 150.0, 135.6, 111.5, 88.5, 82.5, 47.7, 42.7,
41.7, 29.7, 22.7, 14.1, 12.7; 77Se NMR (76 MHz,
CDCl3): d 502, 301; HRESIMS: calcd for C10H12-
N2O3Se2 (M+Na+): 390.9076, obsd: m/z 390.9083.
3.2.1. Bis-(50-deoxy-20,30-O-isopropylidene-uridine) 50,50-
disulfide (5). Starting from 4 (0.1 g, 0.23 mmol); white
25
solid (0.11 g, 77%); mp 175 ꢁC; ½aꢂD ꢀ2.0 (c 1, MeOH);
3.3.2. Bis-(50-deoxy-20,30-O-isopropylidene-uridine)-50,50-
diselenide (10).8 Starting from 4 (0.1 g, 0.23 mmol);
1H NMR (300 MHz, CDCl3): d 9.63 (s, 1H), 7.28–7.25
(aromatic, 2H), 5.75 (br d, 1H, J1 = 1.2 Hz,
25
yellow solid (0.07 g, 74%); mp: 73 ꢁC (decomp); ½aꢂD

K. Sivapriya et al. / Carbohydrate Research 342 (2007) 1151–1158
1157
30 (c 1, CHCl3), 1H NMR (400 MHz, CDCl3): d 8.96 (s,
1H), 7.26 (aromatic, 2H), 5.75 (d, 1H, J = 8.0 Hz), 5.57
(d, 1H, J = 1.6 Hz), 5.09 (dd, 1H, J1 = 1.7 Hz,
J2 = 6.5 Hz), 4.84 (dd, 1H, J1 = 3.9 Hz, J2 = 6.4 Hz),
4.39–4.34 (m, 1H), 3.37–3.28 (m, 2H), 1.57 (s, 3H),
1.37 (s, 3H); 13C NMR (75 MHz, CDCl3): d 164.1,
149.8, 149.2, 115.1, 113.8, 101.5, 94.0, 86.6, 86.5, 83.9,
83.1, 31.1, 26.0, 24.1; 77Se NMR (76 MHz, CDCl3): d
291; HRESIMS: calcd for (M+Na+): 717.0190,
observed: m/z 717.0189.
3.4.2. 50-S-[(2-Acetamido-2-methoxycarbonyl)ethylthio]-
30-O-acetyl-50-deoxythymidine 17. Starting from
8
(0.04 g, 0.07 mmol); colourless, gummy solid, (0.018 g,
61%); 1H NMR (300 MHz, CDCl3): d 8.68 (s, 1H),
7.35 (s, 1H), 6.49 (dd, 1H, J1 = 7.2 Hz, J2 = 7.5 Hz),
6.29–6.21 (m, 1H), 5.30–5.15 (m, 1H), 4.92–4.82 (m,
1H), 4.18–4.14 (m, 1H), 3.79 (s, 1H), 3.19–2.94 (m,
5H), 2.18 (s, 3H), 2.07 (s, 3H), 1.96 (s, 3H); 13C NMR
(75 MHz, CDCl3): d 171.2, 170.6, 169.9, 163.3, 150.2,
135.1, 111.7, 84.5, 83.4, 75.4, 52.8, 52.3, 37.2, 35.5,
35.4, 23.1, 20.9, 12.6, HRESIMS: calcd for
C18H25N3O8S (M+Na+): 466.1260, obsd: m/z 466.1301.
3.3.3. Methyl (2,3,5-trideoxy-3,5-diseleno-a-D-threo-
pentofuranoside (13). Starting from 12 (0.055 g,
0.23 mmol); orange red crystals (crystallized from
3.4.3.
deoxy-20,30-O-isopropylidene-uridine 19. Starting from
(0.03 g, 0.04 mmol); colourless, gummy solid
50-S-[(2-Tolylsulfonylamido)-cyclohexylthio]-50-
25
CHCl3, MeOH mixture, 0.04 g, 88%); mp: 63 ꢁC; ½aꢂD
1
89 (c 1, CHCl3); H NMR (300 MHz, CDCl3): d 5.10
5
1
(d, 1H, J = 4.5 Hz), 4.34 (dt, 1H, J1 = 2.1 Hz,
J2 = 6.6 Hz), 4.19 (dd, 1H, J1 = 1.8 Hz, J2 = 5.7 Hz),
3.39 (s, 3H), 3.09 (dd, 2H, J1 = 2.1 Hz, J2 = 6.3 Hz),
2.24–2.16 (m, 1H), 2.06–2.01 (m, 1H); 13C NMR
(75 MHz, CDCl3): d 105.3, 86.6, 74.8, 54.9, 40.6, 32.7;
77Se NMR (76 MHz, CDCl3): d 290, 430; HRESIMS:
calcd for C6H10O2Se2 (M+): 273.9011, obsd: m/z
273.9004.
(0.017 g, 72%); H NMR (300 MHz, CDCl3): d 9.24 (s,
1H), 7.83–7.23 (aromatic, 5H), 5.89 (d, 1H,
J = 2.7 Hz), 5.62–5.57 (m, 1H), 5.43 (dd, 1H,
J1 = 2.4 Hz, J2 = 6.0 Hz), 5.11–5.05 (m, 1H), 4.38–4.31
(m, 1H), 3.11–2.97 (m, 2H), 2.44 (s, 3H), 2.20–2.06 (m,
2H), 1.70 (s, 3H), 1.60 (s, 3H), 1.42 (s, 3H), 1.27–1.10
(m, 5H); 13C NMR (75 MHz, CDCl3): d 166.7, 163.4,
150.1, 143.3, 137.5, 129.6, 127.2, 114.5, 102.8, 95.9,
88.2, 84.5, 83.5, 82.9, 56.0, 54.8, 53.4, 41.9, 36.9, 27.1,
26.3, 25.2, 23.9, 21.5.
3.4. General procedure for the synthesis of compounds 15,
17 and 19
Acknowledgements
To a stirred soln of the disulfides 5 or 8 in MeCN (2 ml),
benzyltriethylammonium tetrathiomolybdate 1 (0.05 g,
0.08 mmol) was added and the reaction mixture was stir-
red for 3 h at 28 ꢁC. To this mixture a soln of the epox-
ide 14 (0.02 g) in MeCN (0.5 ml) or the unsaturated ester
16 (0.02 g in 0.4 ml of MeCN) or aziridine derivative 18
(0.02 g in 0.5 ml of MeCN) was added slowly in drops.
After the disappearance of the starting material (TLC),
the solvent was removed under diminished pressure and
the black residue was extracted with MeOH–CH2Cl2
(1:9, 5 · 20 ml) and filtered through a Celite pad. The fil-
trate was concentrated and the crude product were puri-
fied by flash column chromatography on silica gel (230–
400 mesh, elution with MeOH–CHCl3 1:9) to furnish the
compounds 15, 17 or 19.
The authors thank DST, New Delhi, for CCD X-ray
facility and Vijay Thiruvenkatam for his help in solving
the molecular structures.
Supplementary data
Characterization data (1H, 13C, HRESIMS) for 5, 8, 9,
10, 13, 15, 17 and 77Se NMR for 9, 10 and 13. Crystal-
lographic information file (CIF) for the compounds 8, 9
and 13, can be found in the online version of this article.
Crystallographic data for 8, 9 and 13 have been depos-
ited with the Cambridge crystallographic data centre
as supplementary publication nos. [a] Compound-8
CCDC-623425, [b] Compound-9 CCDC-606051, [c]
Compound-13 CCDC-606052. Copies of the data can
be obtained free of charge on application to CCDC,
12 Union Road, Cambridge, CB2 1EZ, UK, +44 1223
336408; e-mail: deposit@ccdc.cam.ac.uk. Supplemen-
tary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2007.02.035.
3.4.1. 50-S-[(2-Hydroxy)cyclohexylthio]-30-O-acetyl-50-
deoxythymidine 15. Starting from
8
(0.04 g,
0.07 mmol); colourless, gummy solid (0.02 g, 0.04 mmol,
64%); 1H NMR (300 MHz, CDCl3): d 8.92 (s, 1H), 7.38
(s, 1H), 6.29–6.24 (m, 1H), 5.35–5.31 (m, 1H), 4.30–4.25
(m, 1H), 3.26–3.16 (m, 3H), 2.62–2.21 (m, 2H), 2.12 (s,
1H), 1.96 (s, 1H), 1.77–1.30 (m, 5H), 1.34–1.25 (m,
5H); 13C NMR (75 MHz, CDCl3): d 170.7, 163.4,
150.2, 135.1, 111.6, 84.7, 83.2, 75.3, 71.4, 58.5, 43.3,
37.2, 34.3, 31.9, 31.8, 26.0, 24.3, 20.9, 12.6. HRESIMS:
calcd for C18H26N2O6S (M+Na+): 453.1130; obsd: m/z
453.1138.
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