Synthesis of the â-Anomer of 4′-Thionucleosides
NaHCO3. Silica gel column chromatography of the organic
layer gave 5 (113 mg, 80%) as a syrup. UV (MeOH) λmax 236
nm (ꢀ 3900); 1H NMR (CDCl3) δ 0.06, 0.07, 0.10 and 0.11 (12H,
and J 5a,5b ) 12.2 Hz), 4.67-4.72 (1H, m), 5.27 (1H, d, J 1,2a )
4.6 Hz). δ minor isomer (CDCl3+D2O) δ 1.03-1.13 (28H, m),
2.30 (1H, ddd, J 1,2a ) 3.6, J 2a,3 ) 5.2 and J 2a,2b ) 11.0 Hz),
2.38-2.45 (1H, m), 3.63 (1H, dd, J 4.5a ) 8.4 and J 5a,5b ) 11.6
Hz), 3.77 (1H, dt, J 3,4 ) J 4,5b ) 4.0 and J 4,5a ) 8.4 Hz), 4.00
(1H, dd, J 4,5b ) 4.0 and J 5a,5b ) 11.6 Hz), 4.67-4.72 (1H, m),
5.48 (1H, dd, J 1,2a ) 3.6 and J 1,2b ) 5.0 Hz); FAB-MS m/z 393
(M+ + H), 375 (M+ - OH). Anal. Calcd for C17H36O4SSi2: C,
51.99; H, 9.24. Found: C, 52.05; H, 9.39.
each as s), 0.89 and 0.90 (18H, each as s), 3.45 (1H, dd, J 4,5a
)
9.2 and J 5a,5b ) 10.1 Hz), 3.59 (1H, ddd, J 3,4 ) 2.2, J 4,5a ) 9.2
and J 4,5b ) 6.5 Hz), 3.69 (1H, dd, J 4,5b ) 6.5 and J 5a,5b ) 10.1
Hz), 5.02 (1H, dd, J 3,4 ) 2.2 and J 2,3 ) 3.1 Hz), 5.58 (1H, dd,
J 2,3 ) 3.1 and J 1,2 ) 5.8 Hz), 6.33 (1H, d, J 1,2 ) 5.8 Hz); FAB-
t
MS m/z 303 (M+ - Bu). Anal. Calcd for C17H36O2SSi2: C,
56.61; H, 10.06. Found: C, 53.88; H, 9.95.
1,4-An h yd r o-2-d eoxy-3,5-O-(1,1,3,3-t et r a isop r op yld i-
siloxa n -1,3-d iyl)-4-t h io-D-er yth r o-p en t -1-en it ol (9). To a
stirred solution of 8 (1.25 g, 3.17 mmol) and Et3N (3.03 mL,
22.2 mmol) in CH2Cl2 (20 mL) was added MsCl (1.23 mL, 15.9
mmol) at 0 °C under Ar atmosphere, and the mixture was
stirred at 45 °C for 4 h. The reaction mixture was partitioned
between CHCl3 and sat. NaHCO3. Silica gel column chroma-
tography (hexane/ethyl acetate ) 400/1) of the organic layer
gave 9(800 mg, 67%) as a syrup. UV (MeOH) λmax 237 nm (ꢀ
4500); 1H NMR (CDCl3) δ 1.04-1.11 (28H, m), 3.79 (1H, t, J 4,5a
Ben zyl 2-Deoxy-1,4-dith io-3,5-O-(1,1,3,3-tetr a isopr opyl-
d isiloxa n e-1,3-d iyl)-D-er yth r o-p en tofu r a n osid e (6). The
reaction was carried out according to the procedure described
for the preparation of 2 starting from 1 (6.22 g, 14.2 mmol),
BBr3(1.0 M in CH2Cl2, 3.77 mL, 39.9 mmol), 1,3-dichloro-
1,1,3,3-tetraisopropyldisiloxane (6.83 mL, 21.4 mmol) and
imidazole (3.88 g, 57.0 mmol). Usual workup and silica gel
column chromatography (hexane/ethyl acetate ) 100/1) of the
crude mixture gave 6 (4.76 g, 70%, a mixture (9/1)of diaster-
eomers) as a syrup.
) J 5a,5b ) 11.3 Hz), 3.85-3.89 (1H, m), 4.09 (1H, dd, J 4,5b
)
1H NMR (CDCl3) major-isomer δ 0.95-1.07 (28H, m), 2.24
(1H, ddd, J 1,2a ) 1.2, J 2a,3 ) 5.5 and J 2a,2b ) 12.8 Hz), 2.36
(1H, ddd, J 1,2b ) 6.4, J 2b,3 ) 10.7 and J 2a,2b ) 12.8 Hz), 3.30
(1H, ddd, J 3,4 ) 7.8, J 4,5b ) 3.1 and J 4,5a ) 5.6 Hz), 3.80 (2H,
s), 3.90 (1H, dd, J 4.5a ) 5.6 and J 5a,5b ) 12.1 Hz), 4.02 (1H, dd,
J 4,5b ) 3.1 and J 5a,5b ) 12.1 Hz), 4.14 (1H, dd, J 1,2a ) 1.2 and
J 1,2b ) 6.4 Hz), 4.69 (1H, ddd, J 2a,3 ) 5.5, J 2b,3 ) 10.7 and J 3,4
) 7.8 Hz), 7.21-7.25, 7.27-7.32 (5H, each as m). minor-isomer
4.0 and J 5a,5b ) 11.3 Hz), 5.42-5.44 (1H, m), 5.56 (1H, dd, J 2,3
) 2.5 and J 1,2 ) 5.8 Hz), 6.22 (1H, dd, J 1,2 ) 5.8 and J 1,3 ) 1.6
Hz); FAB-MS m/z 375 (M+ + H). Anal. Calcd for C17H34O3-
SSi2: C, 54.49; H, 9.15. Found: C, 54.62; H, 9.13.
Ben zyl 2-Deoxy-3,5-O-(d i-ter t-bu tylsilylen e)-1,4-d ith io-
D-er yth r o-p en tofu r a n osid e (10). The reaction was carried
out according to the procedure described for the preparation
of 2 starting from 1 (888 mg, 2.03 mmol), BBr3 (1.0 M CH2Cl2
solution) (0.48 mL, 5.09 mmol), di-tert-butylsilyl bis(trifluoro-
methanesulfonate) (0.74 mL, 2.03 mmol), and imidazole (291
mg, 4.27 mmol). Usual workup and silica gel column chroma-
tography (hexane/ethyl acetate ) 70/1) of the crude product
gave 10 (625 mg, 77%, a mixture (6.6/1)of diastereomers) as a
syrup. UV (MeOH) λsh 266 nm (ꢀ 4200), λsh 259 nm (ꢀ 2700);
1H NMR (CDCl3) major-isomer δ 0.98 and 1.07 (18H, each as
s), 2.14 (1H, ddd, J 1,2a ) 7.6, J 2a,3 ) 11.6 and J 2a,2b ) 12.7 Hz),
2.04 (1H, dd, J 2b,3 ) 15,2 and J 2a,2b ) 12.7 Hz), 3.30 (1H, ddd,
J 3,4 ) 9.5, J 4,5b ) 4.6 and J 4,5a ) 11.0 Hz), 3.77 and 3.81 (2H,
each as s), 4.02 (1H, dd, J 4.5a ) 11.0 and J 5a,5b ) 10.1 Hz), 4.18
(selected data). δ 0.93-1.12 (28H, m), 2.01 (1H, ddd, J 1,2a
)
9.5, J 2a,3 ) 10.4 and J 2a,2b ) 12.5 Hz), 2.52 (1H, dt, J 2b,3 ) J 1,2b
) 7.0 and J 2a,2b ) 12.5 Hz), 3.40-3.43 (1H, m), 4.07 (1H, dd,
J 4,5b ) 3.1 and J 5a,5b ) 12.5 Hz), 4.22 (1H, dd, J 1,2a ) 9.5 and
J 1,2b ) 7.0 Hz), 4.22-4.27 (1H, m), 7.23-7.32 (5H, m); FAB-
MS m/z 537 (M+ + K), 455 (M+
-
iPr). Anal. Calcd for
C
24H42O3S2Si2: C, 57.78; H, 8.49. Found: C, 57.83; H, 8.64.
1-O -Ac e t y l-2-d e o x y -3,5-O -(1,1,3,3-t e t r a is o p r o p y l-
d isiloxa n e-1,3-d iyl)-4-th io-D-er yth r o-p en tofu r a n ose (7).
The reaction was carried out according to the procedure
described for the preparation of 3 starting from 6 (2.36
g, 4.74 mmol), AcOH (42.3 mL, 739 mL) and Hg(OAc)2
(3.17 g, 9.95 mmol). Usual workup and silica gel column
chromatography (hexane/ethyl acetate ) 100/1) of the crude
product gave 7 (1.82 g, 88%, a mixture (1.1/1)of epimers)
as a syrup.
(1H, d, J 1,2a ) 7.6 Hz), 4.24 (1H, dd, J 4,5b ) 4.6 and J 5a,5b
)
10.1 Hz), 4.46 (1H, ddd, J 2a,3 ) 11.6, J 2b,3 ) 5.2 and J 3,4 ) 9.5
Hz), 7.23-7.27, 7.28-7.33 (5H, each as m); minor-isomer δ
0.99 and 1.03 (18H, each as s), 1.84 (1H, ddd, J 1,2a ) 9.8, J 2a,3
) 11.0 and J 2a,2b ) 12.4 Hz), 2.65 (1H, m), 3.49 (1H, dd, J 3,4
)
1H NMR (CDCl3) major-isomer δ 1.04-1.09 (28H, m), 2.02
(3H, s), 2.27 (1H, ddd, J 1,2a ) 4.8, J 2a,3 ) 11.6 and J 2a,2b ) 13.0
Hz), 2.38 (1H, dd, J 2b,3 ) 5.2 and J 2a,2b ) 13.0 Hz), 3.25 (1H,
ddd, J 3,4 ) 8.6, J 4,5b ) 2.8 and J 4,5a ) 4.0 Hz), 3.84 (1H, dd,
J 4.5a ) 4.0 and J 5a,5b ) 12.4 Hz), 4.06 (1H, dd, J 4,5b ) 2.8 and
J 5a,5b ) 12.4 Hz), 4.63 (1H, ddd, J 2a,3 ) 11.6, J 2b,3 ) 5.2 and
J 3,4 ) 8.6 Hz), 5.87 (1H, d, J 1,2a ) 4.8 Hz). minor-isomer δ
major-isomer δ 1.04-1.09 (28H, m), 2.06 (3H, s), 2.17 (1H, ddd,
J 1,2a ) 6.0, J 2a,3 ) 10.4 and J 2a,2b ) 13.2 Hz), 2.69 (1H, dt, J 1,2b
) J 2b,3 ) 6.8 and J 2a,2b ) 13.2 Hz), 3.40 (1H, dt, J 3,4 ) 8.8 and
9.5, J 4,5a ) 11.3, and J 4,5b ) 4.6), 3.77 and 3.81 (2H, each as d,
J gem ) 13.8 Hz), 3.91 (1H, dd, J 4,5a ) 11.3 and J 5a,5b ) 10.1
Hz), 4.10 (1H, ddd, J 2a,3 ) 11.0, J 2b,3 ) 6.1, and J 3,4 ) 9.5 Hz),
4.23-4.28 (1H, m), 7.23-7.33 (5H, m); FAB-MS m/z 396 (M+).
Anal. Calcd for C20H32O2S2Si: C, 60.56; H, 8.13. Found: C,
60.68; H, 8.18.
1,4-An h ydr o-2-deoxy-3,5-O-(di-ter t-bu tylsilylen e)-4-th io-
D-er yth r o-p en t -1-en it ol (11) (p r ep a r ed fr om 5). Tetra-
butylammonium fluoride (177 mg, 0.68 mmol) was added to a
solution of 5 (111 mg, 0.31 mmol) in THF (5 mL) at 0 °C under
Ar atmosphere, and the mixture was stirred for 0.5 h. The
reaction mixture was evaporated to dryness, and the residue
was chromatographed on a silica gel (1% MeOH in CH2Cl2) to
give the diol, which was silylated with di-tert-butylsilyl bis-
(trifluoromethanesulfonate) (95 µL, 0.26 mmol) and (dimethyl-
amino)pyridine (63.4 mg, 0.52 mmol) in DMF (4 mL) at 0 °C
under Ar atmosphere overnight. The reaction mixture was
diluted with ehtyl acetate and washed with sat. NaHCO3 and
H2O. Silica gel column chromatography (hexane/ethyl acetate
) 100/1) of the organic layer gave 11 (30.9 mg, 49%) as a solid.
mp 68-69 °C; UV (MeOH) λmax 242 nm (ꢀ 4100), λmin 220 nm
(ꢀ 980); 1H NMR (CDCl3) δ 1.03 and 1.06 (18H, each as s),
3.81-3.87 (1H, m) 4,29 (1H, t, J 4,5a ) J 5a,5b ) 10.1 Hz), 4.33
J 4,5b ) J 4,5a ) 3.1 Hz), 3.84 (1H, dd, J 4.5a ) 3.1 and J 5a,5b
)
12.5 Hz), 4.08 (1H, dd, J 4,5b ) 2.8 and J 5a,5b ) 12.4 Hz), 4.27
(1H, ddd, J 2a,3 ) 10.4 and J 2b,3 ) 6.8 and J 3,4 ) 8.8 Hz), 5.99
(1H, dd, J 1,2a ) 6.0 and J 1,2b ) 6.8 Hz); FAB-MS m/z 473 (M+
+ K), 375 (M+ - OAc). Anal. Calcd for C19H38O5SSi2: C, 52.49;
H, 8.81. Found: C, 52.55; H, 9.19.
2-Deoxy-3,5-O-(1,1,3,3-tetr aisopr opyldisiloxan e-1,3-diyl)-
4-th io-D-er yth r o-p en tofu r a n ose (8). The reaction was car-
ried out according to the procedure described for the prepa-
ration of 3 starting from 7 (197 mg, 0.45 mmol) and methanolic
ammonia (20 mL). Usual workup and silica gel column
chromatography (hexane/ethyl acetate ) 20/1) of the crude
product gave 8 (170 mg, 95%, a mixture (2.8/1) of epimers) as
a syrup. 1H NMR (CDCl3+D2O) major-isomer δ 1.03-1.13
(1H, dd, J 4,5b ) 0.6 and J 5a,5b ) 10.1 Hz), 5.11 (1H, ddd, J 1,3
)
(28H, m), 2.19 (1H, ddd, J 1,2a ) 4.6, J 2a,3 ) 12.6 and J 2a,2b
)
2.5, ) 2.7 and J 3,4 ) 12.2 Hz), 5.86 (1H, dd, J 2,3 ) 2.7 and
J 2,3
11.8 Hz), 2.40 (1H, dd, J 2b,3 ) 5.5 and J 2a,2b ) 11,8 Hz), 3.31
(1H, ddd, J 3,4 ) 8.0, J 4,5b ) 3.1 and J 4,5a ) 5.2 Hz), 3.88 (1H,
dd, J 4.5a ) 5.2 and J 5a,5b ) 12.2 Hz), 4.07 (1H, dd, J 4,5b ) 3.1
J 1,2 ) 6.1 Hz), 6.19 (1H, dd, J 1,3 ) 2.5 and J 1,2 ) 6.1 Hz); FAB-
MS m/z 273 (M+ + H), 215 (M+
-
tBu). Anal. Calcd for
C13H24O2SSi: C, 57.30; H, 8.88. Found: C, 57.54; H, 9.10.
J . Org. Chem, Vol. 67, No. 17, 2002 5923