H. Taniike et al. / Tetrahedron 67 (2011) 7977e7982
7981
(ddd, 1H, J¼3.3, 4.0, and 9.2 Hz), 3.04 (dd, 1H, J¼4.6 and 11.2 Hz),
2.84 (dd, 1H, J¼1.3 and 11.2 Hz), 2.04 (br s, 1H, exchangeable with
12H), 3.70 (d, 2H, J¼11.3 Hz), 1.10e0.99 (m, 56H); 13C NMR (CDCl3)
d
197.77, 164.99, 162.08, 134.37, 111.03, 104.61, 98.94, 80.60, 73.74,
D2O), 1.09e0.82 (m, 28H); 13C NMR (CDCl3)
d
79.42, 75.92, 61.05,
62.72, 55.94, 55.67, 50.54, 17.71, 17.51, 17.45, 17.40, 17.34, 17.30, 13.57,
13.52, 12.79, 12.75; IR (neat) 1725 [C(]O)-O, C(]O)-H], 1608, 1465
(Ar) cmꢀ1; FBMS-LR m/z¼1261 (MNaþ); FABMS-HR calcd for
C52H86O16Si4Se2Na 1261.3221, found 1261.3228.
43.72, 22.92, 17.56, 17.50, 17.47, 17.38, 17.34, 17.30, 17.24, 13.60, 13.52,
13.29, 12.83, 12.79; IR (neat) 3567 (OH) cmꢀ1; FABMS-LR m/z¼441
(MHþ).; FABMS-HR calcd for C17H37O4Si2Se 441.1395, found
441.1391.
Physical data for 9: 1H NMR (CDCl3)
d
7.94 (d, 0.6H, J¼9.4 Hz),
7.78 (d, 0.4H, J¼9.3 Hz), 6.48e6.42 (m, 2H), 6.10 (m, 0.4H), 6.02 (m,
0.6H), 5.02 (dd, 0.6H, J¼3.2 and 10.0 Hz), 4.58 (m, 1H), 4.56 (dd,
0.4H, J¼3.1 and 13.1 Hz), 4.31 (dd, 0.4H, J¼3.3 and 13.3 Hz), 4.22 (m,
0.6H), 4.20 (m, 0.4H), 3.88e3.81 (m, 6.6H), 3.58 (m, 0.6H), 3.41 (dd,
0.4H, J¼5.0 and 14.3 Hz), 3.34 (m, 0.4H), 2.89 (m, 0.4H), 2.86 (m,
0.6H), 1.19e0.91 (m, 28H); ESIMS-LR m/z¼621 (MHþ).
3.1.4. 1,4-Anhydro-2-O-(2,4-dimethoxybenzoyl)-3,5-O-(1,1,3,3-
tetraisopropyldisiloxane-1,3-diyl)-4-seleno- -ribitol (8). To a solu-
D
tion of 7 (4.4 g, 10.0 mmol) in dry pyridine (100 mL) was added 2,4-
dimethoxybenzoyl chloride (4.4 g, 22.0 mmol) at 0 ꢁC, and the
mixture was stirred at room temperature for 30 h. The reaction was
quenched by addition of ice, and the mixture was partitioned be-
tween AcOEt and H2O. The separated organic layer was washed
with saturated aqueous NaHCO3 (three times), followed by brine.
The organic layer was dried (Na2SO4) and concentrated in vacuo,
and the residue was purified by a silica gel column, eluted with
hexane/AcOEt (20:1 to 6:1), to give 8 (5.9 g, 98% as a colorless oil):
The Pummerer-like reaction using iodosylbenzene: to a sus-
pension of uracil (44 mg, 0.4 mmol) in dichloroethane (2 mL) were
added 2,6-lutidine (90
mL, 0.8 mmol) and TMSOTf (290 mL,
1.6 mmol), and the mixture was stirred at room temperature until
giving a clear solution. The resulting solution containing silylated
uracil was added to a solution of 8 (120 mg, 0.2 mmol) in di-
chloroethane (2 mL) containing iodosylbenzene (52 mg,
1H NMR (CDCl3)
d
7.90 (d, 1H, J¼9.2 Hz), 6.50 (m, 2H), 5.80 (m, 1H),
4.33 (dd,1H, J¼3.3 and 9.9 Hz), 4.12 (dd,1H, J¼2.9 and 12.8 Hz), 3.97
(dd, 1H, J¼3.0 and 12.8 Hz), 3.87 (m, 7H,), 3.19 (dd, 1H, J¼4.3 and
0.24 mmol) dropwise. Then, an additional 2,6-lutidine (90 mL,
0.8 mmol) in dichloroethane (1 mL) was added dropwise to the
reaction mixture. The whole was heated at 50 ꢁC for 1.5 h, and the
reaction was quenched by addition of ice. The reaction mixture was
partitioned between AcOEt and H2O. The separated organic layer
was washed with saturated aqueous NaHCO3, followed by brine.
The organic layer was dried (Na2SO4) and concentrated in vacuo.
The residue was purified by a silica gel column, eluted with hexane/
AcOEt (3:1 to 1:1), to give 10 (91 mg, 64% as a white foam) together
with 8 (16 mg, 13%).
11.5 Hz), 2.87 (m, 1H), 1.11e0.91 (m, 28H); 13C NMR (CDCl3)
d 171.18,
164.70, 164.34, 161.60, 133.96, 112.52, 104.51, 98.93, 76.11, 60.43,
59.79, 55.98, 55.51, 44.49, 21.56, 21.08, 17.47, 17.43, 17.35, 17.33,
17.15, 17.12, 14.24, 13.50, 13.13, 12.76; IR (neat) 1728 [C(]O)eO],
1608, 1505 (Ar) cmꢀ1; FABMS-LR m/z¼605 (MHþ).; FABMS-HR
calcd for C26H45O7Si2Se 605.1870, found 605.1873.
3.1.5. 1-[2-O-(2,4-Dimethoxybenzoyl)-3,5-O-(1,1,3,3-tetraiso-
propyldisiloxane-1,3-diyl)-4-seleno-b-D-ribofuranosyl]uracil (10). The
Pummerer-like reaction via 9: ozone was bubbled through a solution
of 8 (120 mg, 0.2 mmol) in CH2Cl2 (5 mL) at ꢀ78 ꢁC. After 10 min, N2
gas was bubbled through the solution to remove excess ozone. The
reaction mixture was allowed to warm to room temperature and
concentrated in vacuo. The reaction mixture was dried (Na2SO4) and
concentrated in vacuo to give 9 as a colorless oil. To a suspension of
3.1.6. 1-(4-Seleno-b-D
-ribofuranosyl)uracil (12)15. To a solution of
10 (360 mg, 0.5 mmol) in THF (4 mL) was added TBAF (1 M in THF,
1.5 mL, 1.5 mmol) at 0 ꢁC. After being stirred for 1 h at room tem-
perature, the reaction mixture was concentrated in vacuo. After
short column purification, the resulting product was dissolved in
methylamine in MeOH (40%, 4 mL), and the mixture was kept for
3 h at room temperature. The solvent was removed in vacuo, and
the residue was coevaporated with MeOH. The residue was purified
by a silica gel column, eluted with MeOH in CHCl3 (5e10%), to give
12 (108 mg, 66% in two steps as a pale yellow foam). An analytical
sample was crystallized from H2O to give pale yellow crystals: mp
uracil (44 mg, 0.4 mmol) in toluene (1.3 mL) were added Et3N (110
mL,
0.8 mmol) and TMSOTf (290 L, 1.6 mmol), and the mixture was
m
stirred at room temperature until giving a clear solution. Additional
CH2Cl2 (0.7 mL) was added to the above solution, which gave a one-
phase clear solution, and the whole was added to a solution of 9 in
dry CH2Cl2 (1.3 mL) dropwise. An additional Et3N (110
mL, 0.8 mmol)
199 ꢁC (lit.15 mp 198e200 ꢁC); 1H NMR (DMSO-d6)
d 11.32 (br s, 1H,
in toluene (0.7 mL) was added dropwise. After being stirred for
15 min at room temperature, the reaction was quenched by addition
of ice, and the reaction mixture was partitioned between AcOEt and
H2O. The separated organic layer was washed with saturated aque-
ous NaHCO3, followed by brine. The organic layer was dried (Na2SO4)
and concentrated in vacuo. The residue was purified by a silica gel
column, eluted with hexane/AcOEt (9:1 to 1:1), to give 10 (53 mg,
36% as a white foam), 11 (10 mg, 4% as a yellow oil), and 8 (23 mg,
19%).
exchangeable with D2O), 7.95 (d, 1H, J¼8.0 Hz), 6.05 (d, 1H,
J¼8.6 Hz), 5.69 (d, 1H, J¼8.0 Hz), 5.41 (d, 1H, J¼6.3 Hz, exchangeable
with D2O), 5.27 (d, 1H, J¼4.0 Hz, exchangeable with D2O), 5.16 (t,
1H, J¼5.2 Hz, exchangeable with D2O), 4.23 (ddd, 1H, J¼3.4, 6.3, and
8.6 Hz), 4.13 (ddd, 1H, J¼1.7, 3.4, and 4.0 Hz), 3.74 (ddd, 1H, J¼5.2,
8.0, and 11.5 Hz), 3.58 (ddd, 1H, J¼5.2, 6.3, and 11.5 Hz), 3.32 (ddd,
1H, J¼1.7, 6.3, and 8.0 Hz); 13C NMR (DMSO-d6)
d 163.01, 151.11,
142.24, 102.24, 77.28, 73.70, 63.91, 55.46, 49.13; IR (KBr) 3184 (NH,
OH), 1671 (C]O), 1605 (C]C) cmꢀ1; FABMS-LR m/z¼309 (MHþ).
Anal. Calcd for C9H12N2O5Se: C, 35.19; H, 3.94; N, 9.12. Found: C,
35.11; H, 3.87; N, 9.00.
Physical data for 10: 1H NMR (CDCl3)
d 8.10 (br s, 1H, ex-
changeable with D2O), 8.04 (d, 1H, J¼8.6 Hz), 7.85 (d, 1H, J¼8.6 Hz),
6.49 (m, 2H), 6.15 (d, 1H, J¼1.1 Hz), 5.73 (dd, 1H, J¼2.7 and 8.6 Hz),
5.67 (dd, 1H, J¼1.1 and 4.0 Hz), 4.55 (m, 1H), 4.19 (dd, 1H, J¼2.9 and
12.5 Hz), 4.05 (m,1H), 3.97 (m,1H), 3.86 (s, 6H),1.15e0.87 (m, 28H);
3.1.7. 1-[2-O-(2,4-Dimethoxybenzoyl)-3,5-O-(1,1,3,3-tetraiso-
propyldisiloxane-1,3-diyl)-4-seleno-
(13). To a solution of 10 (573 mg, 0.8 mmol) in CH3CN (8 mL) in-
cluding Et3N (336 L, 2.41 mmol) and DMAP (292 mg, 2.39 mmol)
b-D-ribofuranosyl]cytosine
13C NMR (CDCl3)
d 164.70, 163.63, 162.58, 161.80, 149.73, 142.23,
134.13, 111.80, 104.75, 102.60, 99.08, 78.65, 73.44, 58.46, 56.09,
55.66, 55.30, 47.57, 17.58, 17.51, 17.46, 17.26, 17.23, 17.04, 17.02, 13.49,
13.39, 13.11, 12.71; IR (neat) 3202 (NH), 1694 [C(]O)eO, C]O],
1608,1508 (Ar) cmꢀ1; FABMS-LR m/z¼715 (MHþ).; FABMS-HR calcd
for C30H47 N2O9Si2Se 715.1985, found 715.1982.
m
was added TPSCl (724 mg, 2.39 mmol), and the reaction mixture
was stirred for 30 min at room temperature. Then, ammonium
hydroxide (10 mL) was added to the reaction mixture, and the
whole was kept for 3 h. The reaction mixture was partitioned
between AcOEt and H2O. The separated organic layer was washed
with 1 N HCl, saturated aqueous NaHCO3, followed by brine. The
organic layer was dried (Na2SO4) and concentrated in vacuo. The
Physical data for 11: 1H NMR (CDCl3)
d 9.62 (s, 2H), 7.97 (d, 2H,
J¼8.6 Hz), 6.50 (m, 4H, J¼8.6 Hz), 5.71 (s, 2H), 4.57 (d, 2H,
J¼11.3 Hz), 4.43 (d, 2H, J¼11.8 Hz), 4.21 (d, 2H, J¼11.8 Hz), 3.87 (s,