Chiba et al.
H), 3.02 (1H, ddd, J ) 2.8, 8.4, 13.9 Hz, 2′-H), 2.91 (1H, dd, J
) 4.8, 14.5 Hz, 5′′-H), 2.58 (1H, ddd, J ) 7.6, 9.6, 13.9 Hz,
2′′-H); 13C NMR (DMSO-d6) δ 156.08, 152.67, 148.94, 139.55,
119.06, 88.61, 82.31, 40.80, 37.77, 25.99; FABMS (in glycerol)
m/e 284 (M + H)+. HRMS. Calcd for C10H14N5OS2: 284.0640.
Found: 284.0622.
MeI (0.31 mL, 5.0 mmol), and K2CO3 (346 mg, 2.5 mmol) in
anhydrous THF (10 mL) was stirred for 12 h at room
temperature. After removal of the solvent, the residue was
taken up into water and extracted with CHCl3. The organic
layer was dried over anhydrous K2CO3 and then evaporated.
The residue was chromatographed on silica gel (eluent; CHCl3)
to give 13 in 92% yield as a colorless foam. IR (KBr) 3060,
1700, 1040 cm-1; 1H NMR (CDCl3) δ 8.36 (1H, brs, 3-NH), 7.55
(1H, d, J ) 1.0 Hz, 6-H), 7.40 (2H, dd, J ) 0.8, 8.3 Hz, DMTr),
7.20-7.32 (7H, m, DMTr), 6.80-6.83 (4H, m, DMTr), 6.08 (1H,
dd, J ) 5.3, 6.8 Hz, 1′-H), 3.86 (1H, ddd, J ) 4.6, 4.6, 7.5 Hz,
4′-H), 3.80 (6H, s, -OMe), 3.04 (1H, dd, J ) 7.3, 7.3, 7.3 Hz,
3′-H), 2.76 (1H, dd, J ) 4.0, 13.0 Hz, 5′-H), 2.54 (1H, dd, J )
5.0, 13.0 Hz, 5′′-H), 2.26-2.37 (2H, m, 2′-H and 2′′-H), 2.01
(3H, s, -SMe), 1.87 (3H, d, J ) 1.0 Hz, 5-Me); 13C NMR
(CDCl3) δ 163.41, 158.24, 149.94, 145.01, 136.69, 135.71,
130.62, 129.30, 127.99, 126.82, 113.24, 110.75, 84.61, 83.47,
66.11, 55.26, 45.14, 39.22, 35.15, 14.15, 12.50; FABMS (in
3-nitrobenzyl alcohol containing 50% glycerol with NaI) m/e
613 (M + Na)+. HRMS. Calcd for C32H34N2O5S2Na: 613.1807.
Found: 613.1805.
3′,5′-Dith io-2′-d eoxy-r-a d en osin e, 2r. A solution of 11r
(117 mg, 0.16 mmol) in MeOH containing 40%(v/v) MeNH2 (1.0
mL) was stirred for 1.5 h at room temperature. After removal
of the solvent, the residue was dissolved in CH2Cl2 (3.0 mL).
EtSH (1.5 mL, 20 mmol) and Et3N (0.90 mL, 6.7 mmol) were
added to the solution, and the reaction mixture was stirred
for 1.5 h at room temperature. After removal of the solvent,
the residue was chromatographed on silica gel (eluent; CHCl3/
MeOH ) 10:1) to give 2r (reprecipitation from n-hexane) in
12% yield as a colorless solid. Mp 150.5-151.0 °C; IR (KBr)
1
3300, 3140, 2550, 1665, 1600 cm-1; H NMR (CDCl3) δ 8.37
(1H, s, adenine), 7.96 (1H, s, adenine), 6.23 (1H, dd, J ) 6.3,
7.0 Hz, 1′-H), 5.76 (1H, brs, NH2), 4.46 (1H, ddd, J ) 4.3, 4.3,
8.7 Hz, 4′-H), 3.46 (1H, dddd, J ) 9.2, 9.2, 9.2, 9.2 Hz, 3′-H),
3.13 (1H, ddd, J ) 7.3, 8.5, 13.8 Hz, 2′-H), 3.06 (1H, ddd, J )
3.6, 7.3, 14.4 Hz, 5′-H), 2.86 (1H, ddd, J ) 6.1, 9.9, 13.8 Hz,
2′′-H), 2.79 (1H, ddd, J ) 4.7, 9.6, 14.3 Hz, 5′′-H), 2.16 (1H, d,
J ) 9.3 Hz, 3′-SH), 1.60 (1H, dd, J ) 7.3, 9.5 Hz, 5′-SH); 13C
NMR (CDCl3) δ 155.50, 153.01, 149.46, 139.45, 120.51, 87.21
(4′-C), 84.24 (1′-C), 42.12 (2′-C), 38.27 (3′-C), 25.96 (5′-C);
FABMS (in 3-nitrobenzyl alcohol containing 50% glycerol) m/e
284 (M + H)+. HRMS. Calcd for C10H14N5OS2: 284.0640.
Found: 284.0616.
3′-S-Meth yl-3′,5′-d ith io-2′-d eoxyth ym id in e, 4. To a solu-
tion of 13 (413 mg, 0.7 mmol) in THF containing 25%(v/v)
MeOH (16 mL) was added an aqueous solution of NaOAc (1.5
mL, 3.0 M). Separately, a solution of AgNO3 (238 mg, 1.4
mmol) in water (1.0 mL) was diluted with MeOH (5.0 mL),
and the solution was added to 13. The mixture was stirred
for 5 min, the solids were collected by filtration, and the pellet
was washed with three portions of MeOH (each 2 mL) to
remove dimethoxytrityl-containing byproducts. To a suspen-
sion of the pellet in THF containing 50%(v/v) MeOH (40 mL)
was added aqueous NaOAc (1.5 mL, 3.0 M) and dithioeryth-
reitol (DTE, 431 mg, 2.8 mmol). The mixture was stirred for 2
h at room temperature and then filtered through Celite. The
filtrate was evaporated, and the residue was taken up into
water and extracted with CHCl3. The organic layer was
washed with water, dried over anhydrous MgSO4, and then
evaporated. The title compound 4 was obtained in 83% yield
S,S′-Dim eth yl-3′,5′-d ith io-2′-d eoxyth ym id in e, 3. A solu-
tion of 1 (274 mg, 1.0 mmol), MeI (1.25 mL, 20 mmol), and
K2CO3 (8.30 g, 60 mmol) in anhydrous THF (20 mL) was
stirred for 15 h at room temperature. After removal of the
solvent, the residue was taken up into water and extracted
with CHCl3. The organic layer was dried over anhydrous
MgSO4 and then evaporated. The residue was chromato-
graphed on silica gel (eluent; CHCl3) to give 3 in 97% yield as
a colorless oil. IR (KBr) 3180, 1700, 1680, 1060 cm-1; [R]25
D
1
as a colorless oil. IR (KBr) 3190, 2560, 1680, 1060 cm-1; [R]25
+3.03 (c ) 1.00, CH2ClCH2Cl); H NMR (CDCl3) δ 8.81 (1H,
D
1
brs, 3-NH), 7.55 (1H, d, J ) 1.1 Hz, 6-H), 6.17 (1H, dd, J )
4.6, 7.1 Hz, 1′-H), 4.04 (1H, ddd, J ) 4.1, 4.1, 8.3 Hz, 4′-H),
3.30 (1H, ddd, J ) 8.3, 8.3, 8.3 Hz, 3′-H), 3.01 (1H, dd, J )
4.0, 14.4 Hz, 5′-H), 2.89 (1H, dd, J ) 4.5, 14.3 Hz, 5′′-H), 2.40-
2.51 (2H, m, 2′-H and 2′′-H), 2.21 (3H, s, -SMe), 2.17 (3H, s,
-SMe), 1.95 (3H, d, J ) 0.9 Hz, 5-Me); 13C NMR (CDCl3) δ
163.52, 150.15, 135.61, 111.10, 84.45, 83.95, 45.06, 39.38,
37.01, 17.42, 14.28, 12.55; FABMS (in glycerol) m/e 303 (M +
H)+. HRMS. Calcd for C12H19N2O3S2: 303.0837. Found:
303.0847.
+1.92 (c ) 1.00, CH2ClCH2Cl); H NMR (CDCl3) δ 9.54 (1H,
brs, NH), 7.47 (1H, d, J ) 1.2 Hz, 6-H), 6.19 (1H, dd, J ) 4.9,
7.1 Hz, 1′-H), 3.97 (1H, ddd, J ) 4.1, 4.1, 8.1 Hz, 4′-H), 3.32
(1H, ddd, J ) 8.3, 8.3, 8.3 Hz, 3′-H), 3.07 (1H, ddd, J ) 3.8,
8.3, 14.4 Hz, 5′-H), 2.89 (1H, ddd, J ) 4.5, 8.8, 14.4 Hz, 5′′-H),
2.41-2.52 (2H, m, 2′-H and 2′′-H), 2.18 (3H, s, SMe), 1.95 (3H,
d, J ) 1.2 Hz, 5-Me), 1.61 (1H, d, J ) 8.5 Hz, 3′-SH); 13C NMR
(CDCl3) δ 163.45, 150.11, 135.55, 111.22, 84.11, 83.71, 44.23,
39.16, 26.91, 14.18, 12.65; FABMS (in glycerol) m/e 289 (M +
H)+. HRMS. Calcd for C11H17N2O3S2: 289.0681. Found:
289.0638.
5′-S-(4,4′-Dim et h oxyt r it yl)-3′,5′-d it h io-2′-d eoxyt h ym i-
d in e, 12. To a solution of 1 (137 mg, 0.50 mmol) in anhydrous
THF (10 mL) was added pyridine (0.40 mL) and DMTrCl (169
mg, 0.50 mmol) at -20 °C. The reaction mixture was stirred
at -20 °C for 12 h and then evaporated. The residue was
chromatographed on silica gel (eluent; CH2Cl2/AcOEt ) 10:1)
to give 12 in 87% yield as a colorless foam. IR (KBr) 3190,
S-Eth yl-3′-th io-2′-d eoxyth ym id in e, 15. To a suspension
of NaH (154 mg, 6.4 mmol; washed thoroughly with n-hexane
prior to use) in DMA (5.0 mL) was added dropwise EtSH (1.19
mL, 16 mmol) at room temperature. The suspension was
stirred for 30 min at room temperature and then turned to a
clear yellow solution. This solution was added to a solution of
2,3′-anhydro-1-(5′-O-trityl-2′-deoxy-â-D-lyxosyl)thymine, 14,5
(1.50 g, 3.2 mmol) in DMA (20 mL) at room temperature. The
reaction mixture was stirred for 4.5 h at 65 °C. After removal
of the solvent in vacuo, the residue was taken up into water
and extracted with AcOEt. The organic layer was washed with
brine and dried over anhydrous MgSO4. After removal of the
solvent, the residue was dissolved in EtOH (30 mL) and
concentrated HCl (one drop) was added. The reaction mixture
was stirred for 6 h at 85 °C and then evaporated. The residue
was chromatographed on silica gel (eluent; toluene/AcOEt )
1:1) to give 15 in 86% yield as a colorless oil. IR (KBr) 3425,
3180, 1695, 1680, 1060 cm-1; 1H NMR (CDCl3) δ 8.98 (1H, brs,
NH), 7.55 (1H, d, J ) 1.2 Hz, 6-H), 6.11 (1H, dd, J ) 4.1, 7.2
Hz, 1′-H), 4.05 (1H, ddd, J ) 2.3, 4.3, 12.1 Hz, 5′-H), 3.90 (1H,
ddd, J ) 2.4, 2.4, 8.2 Hz, 4′-H), 3.85 (1H, ddd, J ) 2.7, 6.2,
12.1 Hz, 5′′-H), 3.51 (1H, ddd, J ) 8.3, 8.3, 8.3 Hz, 3′-H), 2.70
1700, 1680, 1040 cm-1 1H NMR (CDCl3) δ 8.33 (1H, brs,
;
3-NH), 7.48 (1H, d, J ) 0.5 Hz, 6-H), 7.41 (2H, d, J ) 7.5 Hz,
DMTr), 7.21-7.33 (7H, m, DMTr), 6.81-6.84 (4H, m, DMTr),
6.07 (1H, dd, J ) 3.5, 7.0 Hz, 1′-H), 3.73-3.80 (7H, m, 4′-H
and -OMe), 3.18 (1H, dddd, J ) 8.4, 8.4, 8.4, 8.4 Hz, 3′-H),
2.87 (1H, dd, J ) 4.0, 13.0 Hz, 5′-H), 2.54 (1H, dd, J ) 4.5,
13.0 Hz, 5′′-H), 2.39 (1H, ddd, J ) 3.8, 8.3, 14.3 Hz, 2′-H), 2.25
(1H, ddd, J ) 7.6, 9.6, 14.4 Hz, 2′′-H), 1.85 (3H, d, J ) 0.5 Hz,
5-Me), 1.43 (1H, d, J ) 7.5 Hz, 3′-SH): 13C NMR (CDCl3) δ
163.36, 158.29, 149.93, 144.98, 136.69, 135.67, 130.66, 129.34,
128.06, 126.88, 113.31, 110.81, 86.98, 84.02, 66.22, 55.28,
42.26. 36.86, 33.25, 12.46 ; FABMS (in 3-nitrobenzyl alcohol
containing 50% glycerol with NaI) m/e 599 (M + Na)+. HRMS.
Calcd for C31H32N2O5S2Na: 599.1650. Found: 599.1654.
5′-S-(4,4′-Dim et h oxyt r it yl)-3′-S-m et h yl-3′,5′-d it h io-2′-
d eoxyth ym id in e, 13. A solution of 12 (288 mg, 0.50 mmol),
336 J . Org. Chem., Vol. 68, No. 2, 2003