K. Haraguchi et al. / Tetrahedron 66 (2010) 4587e4600
4597
br); NOE experiment: H-6/H-20 (0.2%) and H-30/H-6 (13.4%); 13C
NMR (CDCl3) 5.2, 6.7, 12.2, 20.6, 22.7, 27.2, 39.6, 67.1, 74.8, 78.1,
81.5, 99.9, 107.7, 127.4, 128.5, 129.6, 137.7, 149.9, 163.8; FABMS (m/z):
730 (MþþH). Anal. Calcd for C31H49IN2O6Si: C, 51.09; H, 6.78; N,
3.84. Found: C, 51.20; H, 6.87; N, 3.57.
BSA (0.8 mL, 3.24 mmol), a CH2Cl2 (10 mL) solution of 42 (463 mg,
1.08 mmol), and NIS (364 mg, 1.62 mmol). Silica gel column chro-
matography (hexane/ethyl acetate¼3:1) of the crude mixture gave
50 (248 mg, 34%) as pale yellow foam: UV (MeOH): lmax 268 nm
d
(
3
9900), lmin 235 nm (
3
2500); [
a
]
20 ꢀ79.3 (c 0.81, CHCl3); IR (neat,
D
Physical data of 48b: UV (MeOH): lmax 271 nm (
3
10,300), lmin
cmꢀ1): 3176, 2931,1697,1471,1388,1365,1319,1286,1192, and 1043;
239 nm (
3
2600); [
a]
20 ꢀ101.4 (c 0.72, CHCl3); IR (neat, cmꢀ1): 3244,
1H NMR (CDCl3)
and 1.08 (18H, each as s), 1.52 and 1.73 (3H, each as s), 1.92 (3H, d, J5-
d
0.53 (6H, q, J¼8.0 Hz), 0.88 (9H, t, J¼8.0 Hz), 1.00
D
3064, 2951, 2935, 2875, 2860, 1699, 1684, 1188, 1151, 1128, 1072,
1045, and 1011; 1H NMR (CDCl3)
J¼8.0 Hz), 1.04 and 1.12 (18H, each as s), 1.56 (3H, d, J5-Me,6¼1.1 Hz),
d
0.44e0.56 (6H, m), 0.86 (9H, t,
¼1.1 Hz), 3.18 (1H, dd, J2 ,3 ¼5.2 Hz and J3 ,4 ¼9.7 Hz), 3.89 (1H,
0
0
0
0
Me,6
0
0
0
0
Jgem¼9.2 Hz and J4 ,5 a¼10.3 Hz), 4.12 (1H, ddd, J4 ,5 b¼5.2 Hz and
0
0
0
0
0
0
0
0
0
0
3.21 (1H, dd, J2 ,3 ¼6.9 Hz and J3 ,4 ¼9.2 Hz), 3.99 (1H, dd,
J3 ,4 ¼J4 ,5 a¼10.9 Hz), 4.47 (1H, dd, J4 ,5 b¼5.2 Hz and Jgem¼9.2 Hz),
0
0
0
0
0
0
Jgem¼9.2 Hz and J4 ,5 a¼10.2 Hz), 4.29 (1H, ddd, J3 ,4 ¼9.2 Hz,
6.60 (1H, d, J2 ,3 ¼5.2 Hz), 7.46 (1H, d, J5-Me,6¼1.1 Hz), 8.93 (1H, br);
J4 ,5 b¼4.2 Hz, and J4 ,5 a¼10.2 Hz), 4.59 (1H, dd, J4 ,5 b¼4.2 Hz and
NOE experiment: H-6/H-20 (0.1%), H-50 (1.4%), H-30 (0.8%); 13C NMR
0
0
0
0
0
0
0
0
Jgem¼9.2 Hz), 5.56 (1H, d, J2 ,3 ¼6.9 Hz), 5.68 (1H, s), 6.88 (1H, d, J5-
(CDCl3) d 6.4, 6.8,12.7, 20.6, 22.8, 27.1, 27.2, 26.8, 28.4, 31.8, 67.1, 74.7,
¼1.1 Hz), 7.17e7.19 and 7.29e7.31 (5H, each as m), 8.44 (1H, br);
77.4, 80.7, 102.9, 108.0, 138.8, 150.6, 164.1; FABMS (m/z): 680 (Mþ).
Anal. Calcd for C27H49IN2O6Si2: C, 47.64; H, 7.25; N, 4.11. Found: C,
47.64; H, 7.40; N, 3.75.
Me,6
NOE experiment; H-6/H-20(0.2%), H-6/H-30 (1.0%) and H-50/H-6
(3.4%); 13C NMR (CDCl3)
d 5.3, 6.9, 12.2, 20.6, 22.7, 27.1, 27.3, 36.9,
67.2, 74.5, 77.4, 78.4, 97.2, 108.3, 127.6, 128.0, 128.8, 134.8, 149.9,
163.4; FABMS (m/z): 730 (MþþH). Anal. Calcd for C31H49IN2O6Si: C,
51.09; H, 6.78; N, 3.84. Found: C, 50.97; H, 6.80; N, 3.60.
4.37. 1-[3,5-O-(Di-tert-butylsilylene)-2-deoxy-2-iodo-1-C-
(triethylsilyloxyethyl)-b-D-ribofuranosyl]thymine (51)
4.35. 1-[3,5-O-(Di-tert-butylsilylene)-2-deoxy-2-iodo-1-C-(
a
-
Compound 51 was prepared as described above for 19 starting
from a CH3CN (2.0 mL) solution of thymine (221 mg, 1.76 mmol)/
BSA (0.9 mL, 3.51 mmol), a CH2Cl2 (12 mL) solution of 43 (486 mg,
1.17 mmol), and NIS (394 mg, 1.76 mmol). Silica gel column chro-
matography (hexane/ethyl acetate¼3:1) of the crude mixture gave
triethylsilyloxyethyl)- -ribofuranosyl]thymine (49a,b)
b-D
Compound 49 was prepared as described above for 19 starting
from a CH3CN (1.0 mL) solution of thymine (115 mg, 0.92 mmol)/
BSA (0.45 mL, 1.83 mmol), a CH2Cl2 (6 mL) solution of 41 (500 mg,
1.05 mmol), and NIS (207 mg, 0.92 mmol). Silica gel column chro-
matography on silica gel (hexane/ethyl acetate¼3:1) of the crude
mixture gave a mixture of 49a and 49b. HPLC separation (hexane/
ethyl acetate¼2.5:1) of the mixture gave 49a (185 mg, 45%, pale
yellow foam, tR¼5.8 min) and 49b (185 mg, 45%, pale yellow foam,
tR¼6.3 min).
51 (450 mg, 58%) as pale yellow foam: UV (MeOH): lmax 271 nm
20
(
3
11,000), lmin 236 nm (
3
2200); [
a
]
ꢀ49.0 (c 0.88, CHCl3); IR
D
(neat, cmꢀ1): 3195, 3047, 2935, 2877, 1697, 1473, 1300, 1244, 1192,
1153, 1095, 1057, and 1012; 1H NMR (CDCl3)
d
0.47 (6H, t, J¼8.0 Hz),
0.87 (9H, t, J¼8.0 Hz), 1.02 and 1.07 (18H, each as s), 1.93 (3H, s, br),
2.35 (1H, dt, J¼4.0 and 14.9 Hz), 2.98 (1H, dt, J¼6.9 and 14.9 Hz),
0
0
0
0
3.21 (1H, dd, J2 ,3 ¼5.7 Hz and J3 ,4 ¼10.3 Hz), 3.58 (2H, dd, J¼4.0 and
0
0
Physical data of 49a: UV (MeOH): lmax 270 nm (
3
11,300), lmin
6.9 Hz), 3.95 (1H, dd, Jgem¼9.2 Hz and J4 ,5 a¼10.3 Hz), 4.13 (1H, dt,
20 ꢀ108.9 (c 0.15, CHCl3); IR (neat, cmꢀ1): 3178,
J4 ,5 b¼4.6 Hz and J3 ,4¼J4 ,5 a¼10.3 Hz), 4.51 (1H, dd, J4 ,5 b¼5.2 Hz
0
0
0
0
0
0
0
237 nm (
3
2300); [
a
]
D
3047, 2935, 2877, 2860, 1670, 1478, 1290, 1192, 1153, and 1070; 1H
and Jgem¼9.2 Hz), 5.56 (1H, d, J2 ,3 ¼5.7 Hz), 7.43 (1H, d, J5-
0
0
NMR (CDCl3)
d
0.45e0.56 (6H, m), 0.87 (9H, t, J¼8.0 Hz), 1.03 and
¼1.1 Hz), 8.72 (1H, br); NOE: H-6/H-20 (0.2%), H-6/H-50 (2.2%)
Me,6
1.07 (18H, each as s), 1.49 (3H, d, J¼6.3 Hz), 1.92 (3H, br), 3.25 (1H,
and H-30/H-6 (2.2%); 13C NMR (CDCl3)
d 4.1, 6.6, 12.8, 20.6, 22.8, 27.1,
0
0
0
0
dd, J2 ,3 ¼5.7 Hz and J3 ,4 ¼8.6 Hz), 3.95e4.03 (2H, m), 4.53 (1H, dd,
27.2, 41.4, 43.4, 58.1, 66.7, 74.4, 76.7, 97.7, 109.6, 134.9, 150.0, 164.0;
FABMS (m/z): 705 (MþþK). Anal. Calcd for C31H50N2O6Si2$1/
2AcOEt: C, 47.31; H, 7.23; N, 3.94. Found: C, 47.42; H, 7.33; N, 3.60.
0
0
J4 ,5 b¼4.0 Hz and Jgem¼8.6 Hz), 4.73 (1H, q, J¼6.3 Hz), 5.73 (1H, d0,
0
0
J2 ,3 ¼5.7 Hz), 7.40 (1H, br), 8.60 (1H, br); NOE experiment: H-6/H-2
(0.3%), H-6/H-30 (1.3%) and H-50/H-6 (3.4%); 13C NMR (CDCl3)
d 5.0,
6.7, 12.6, 19.4, 20.6, 22.7, 27.1, 27.3, 36.5, 67.0, 73.2, 74.2, 77.4, 98.9,
108.7, 136.2, 150.1, 164.0; FABMS (m/z): 667 (MþþH). Anal. Calcd for
C26H47IN2O6Si: C, 46.84; H, 7.11; N, 4.20. Found: C, 46.96; H, 7.19; N,
4.00.
4.38. 1-[3,5-O-(Di-tert-butylsilylene)-2-deoxy-2-iodo-1-C-
(triethylsilyloxypropyl)-b-D-ribofuranosyl]thymine (52)
Compound 52 was prepared as described above for 19 starting
from a CH3CN (2.0 mL) solution of thymine (89 mg, 0.71 mmol)/BSA
(0.4 mL, 1.41 mmol), a CH2Cl2 (4.7 mL) solution of 44 (200 mg,
0.47 mmol), and NIS (158 mg, 0.71 mmol). Silica gel column chro-
matography (hexane/ethyl acetate¼5:1) of the crude mixture gave
Physical data of 49b: UV (MeOH): lmax 267 nm (3 11,200), lmin
20
235 nm (
3
2300); [
a
]
ꢀ87.1 (c 0.67, CHCl3); IR (neat, cmꢀ1): 3172,
D
3060, 2935,1697,1473,1383,1363,1286,1238,1196,1155,1136,1099,
and 1057; 1H NMR (CDCl3)
J¼8.0 Hz), 1.01 and 1.08 (18H, each as s), 1.22 (3H, d, J¼6.3 Hz), 1.90
d
0.61 (6H, q, J¼8.0 Hz), 0.95 (9H, t,
52 (154 mg, 48%) as pale yellow syrup: lmax 268 nm (3 11,700), lmin
(3H, br), 3.25 (1H, dd, J2 ,3 ¼5.2 Hz and J3 ,4 ¼10.9 Hz), 3.87 (1H, dd,
235 nm (3 2500); [a]
20 ꢀ58.5 (c 0.25, CHCl3); IR (neat, cmꢀ1): 3197,
0
0
0
0
D
0
0
0
0
Jgem¼9.2 Hz and J4 ,5 a¼10.9 Hz), 4.19 (1H, dt, J4 ,5 b¼5.2 Hz,
3064, 2951, 2875, 2862, 1699, 1473, 1458, 1286, 1236, 1194, 1151,
J3 ,4 ¼J4 ,5 a¼10.9 Hz), 4.42 (1H, dd, J4 ,5 b¼5.2 Hz and Jgem¼9.2 Hz),
1128, 1093, and 1057; 1H NMR (CDCl3)
d 0.56e0.60 (6H, m),
0
0
0
0
0
0
0
0
4.61 (1H, q, J¼6.3 Hz), 6.66 (1H, d, J2 ,3 ¼5.2 Hz), 7.46 (1H, d, J5-
0.93e0.96 (9H, m), 1.02 and 1.08 (18H, each as s), 1.00e1.08 (1H, m),
1.47e1.55 (1H, m), 1.94 (3H, d, J5-Me,6¼1.1 Hz), 2.65e2.30 (1H, m),
¼1.1 Hz), 9.12 (1H, br); NOE experiment: H-6/H-20(0.3%), H-6/H-
Me,6
30 (1.3%) and H-50/H-6 (3.4%); 13C NMR (CDCl3)
d
4.9, 6.7, 12.5, 19.5,
2.65e2.73 (1H, m), 3.21 (1H, dd, J2 ,3 ¼5.2 Hz and J3 ,4 ¼9.2 Hz),
0
0
0
0
0
0
20.6, 22.8, 27.2, 27.3, 36.7, 67.3, 75.1, 77.6, 77.8, 99.9,108.3,138.8,150.6,
164.4; FABMS (m/z): 679 (MþþH). Anal. Calcd for C26H47IN2O6Si: C,
46.84; H, 7.11; N, 4.20. Found: C, 47.06; H, 7.23; N, 4.00.
3.53e3.61 (2H, m), 4.02 (1H, dd, Jgem¼9.2 Hz and J4 ,5 a¼10.3 Hz),
0
0
0
0
0
4.14 (1H, ddd, J4 ,5 b¼4.6 Hz, J3 ,4¼9.2 Hz, and J4 ,5 a¼10.3 Hz), 4.51
0
0
0
0
(1H, dd, J4 ,5 b¼4.6 Hz and Jgem¼9.2 Hz), 5.56 (1H, d, J2 ,3 ¼5.2 Hz),
7.41 (1H, d, J5-Me,6¼1.1 Hz), 9.07 (1H, br); NOE experiment: H-50/H-6
4.36. 1-[3,5-O-(Di-tert-butylsilylene)-2-deoxy-2-iodo-1-C-(
a-
(7.4%), H-30/H-6 (2.1%) and H-6/H-20 (0.2%); 13C NMR (CDCl3)
d 4.3,
triethylsilyloxy- -methylethyl)- -ribofuranosyl]thymine (50)
a
b
-
D
6.8, 12.8, 20.6, 22.8, 27.1, 27.2, 27.3, 38.2, 40.9, 61.9, 66.6, 74.5, 76.8,
99.0, 109.9, 134.8, 149.5, 164.0; FABMS (m/z): 679 (MþꢀH). Anal.
Calcd for C27H49IN2O6Si2$1/2 AcOEt: C, 48.06; H, 7.37; N, 3.86.
Found: C, 48.15; H, 7.47; N, 3.58.
Compound 50 was prepared as described above for 19 starting
from a CH3CN (2.0 mL) solution of thymine (204 mg, 1.62 mmol)/