S. Honzawa et al. / Tetrahedron 56 (2000) 2615±2627
2623
(1H, m), 7.88±8.02 (2H, m), 8.84±9.10 (1H, br). HRMS m/z
Calcd for C18H20N2O5: 344.1372. Found: 344.1386. [a]2D7
238.0 (c 0.50, CHCl3).
127.6, 127.8, 127.9, 129.67, 129.7, 135.8, 135.96, 136.01,
136.03, 144.7, 144.8, 156.2, 157.7, 158.0, 158.1, 166.2. IR
(KBr) 2930, 1684, 1630, 1537, 1509, 1250 cm21. FAB-MS
m/z 925 (M111). Anal. Calcd for C56H56N6O7´1.5H2O: C,
70.64; H, 6.25; N, 8.83%. Found: C, 70.93; H, 6.55; N,
8.76%. [a]2D3231.3 (c 1.01, CHCl3).
(10S,20S,30R)-1-[20-Benzoyloxymethyl-30-(hydroxymethyl)-
cyclobutyl]thymine (ent-9). [a]2D6137.4 (c 1.03, CHCl3).
(10R,20R,30S)-9-[20-Benzoyloxymethyl-30-(hydroxymethyl)-
cyclobutyl]-N2-isobutyrylguanine (10). Mp 102±1038C
(CHCl3±hexane). 1H NMR (CDCl3) d 1.23 (2H, d,
J6.8 Hz), 2.38 (1H, brs), 2.50±2.61 (2H, m), 2.65±2.71
(3H, m), 3.09±3.16 (1H, m), 3.76±3.85 (2H, m), 4.45±4.59
(3H, m), 7.35 (2H, t, J7.6 Hz), 7.52 (2H, t, J6.8 Hz),
7.81 (1H, s), 7.83 (1H, s), 9.45 (1H, brs), 11.95 (1H, brs).
13C NMR (CDCl3) d 19.0, 19.1, 27.9, 34.1, 36.0, 44.9, 48.6,
63.3, 65.4, 120.7, 128.2, 129.0, 133.0, 137.8, 147.4, 148.6,
155.7, 166.2, 179.5. IR (KBr) 2974, 2936, 2874, 1677, 1607,
1557, 1477, 1400, 1314, 1272 cm21. HRMS (EI) Calcd for
C22H25N505: 439.1856. Found: 439.1855. [a]2D512.15 (c
1.02, CHCl3).
(10S,20S,30RS)-9-{20-Hydroxymethyl-30-[bis(p-methoxy-
phenyl)phenylmethyloxy]cyclobutyl}-N2-(N,N-dimethyl-
aminomethylene)guanine (ent-13). To a solution of ent-12
in MeOH (3 mL) and CHCl3 (3 mL) was added CH3CO2H
(1 mL), and the mixture was stirred for at room temperature
for 3 h. The reaction was quenched by addition of saturated
aqueous NaHCO3 (3 mL), and the organic layer separated
was washed with saturated aqueous NaHCO3 and brine.
After dried over Na2SO4 the solution was concentrated.
Puri®cation by silica gel ¯ash column chromatography
(CHCl3±hexane±MeOH, 10:10:1) gave ent-13 (10 mg,
17%), its regioisomer (14 mg, 24%), and recovery of ent-
12 (51 mg, 58%). ent-13: Mp 127.0±127.28C (CHCl3±
1
Hexane). H NMR (CDCl3, 400 MHz) d 2.00 (1H, brs),
(10R,20R,30S)-1-[20-Benzoyloxymethyl-30-(hydroxymethyl)-
cyclobutyl]-N4-benzoylcytosine (11). Mp 90±918C
(CHCl3±hexane). 1H NMR (CD3OD) d 1.99±2.18 (m,
4H), 2.50 (1H, dt, J7.7, 10.0 Hz), 2.57±2.65 (1H, m),
3.57±3.68 (2H, m), 3.70 (2H, d, J6.0 Hz), 4.60 (1H, q,
J8.4 Hz), 7.50±7.56 (2H, m), 7.58±7.67 (2H, m), 7.94±
7.99 (2H, m), 8.25 (1H, d, J7.2 Hz). 13C NMR (CD3OD) d
29.6, 34.5, 54.6, 64.0, 64.8, 98.3, 128.9, 129.1, 129.6, 130.5,
133.8, 134.4, 147.8, 158.5, 163.9, 168.7. IR (KBr) 3417,
1714, 1650, 1480, 1271 cm21. HRMS (EI) Calcd for
C17H19N3O4: 329.1376. Found: 329.1360. [a]2D4157.4 (c
1.0, CHCl3).
2.16±2.20 (1H, m), 2.28 (1H, q, J9.9 Hz), 2.52±2.59
(1H, m), 2.62±2.66 (1H, m), 3.07 (3H, s), 3.13 (3H, s),
3.10±3.13 (1H, m), 3.25 (1H, dd, J4.7, 9.3 Hz), 3.78
(6H, s), 4.43 (1H, q, J8.3 Hz), 4.70 (1H, brs), 6.82 (4H,
d, J9.0 Hz), 7.20 (2H, t, J8.6 Hz), 7.27±7.31 (5H, m),
7.40 (2H, d, J8.6 Hz), 7.59 (2H, s), 8.46 (1H, s), 9.30 (1H,
brs). 13C NMR (CDCl3, 100 MHz) d 28.3, 32.1, 35.2, 41.4,
49.4, 50.1, 55.2, 60.0, 65.6, 86.1, 113.0, 136.1, 144.7, 149.7,
156.6, 157.6, 158.3. IR (KBr) 3404, 2931, 1681, 1631, 1541,
1509, 1425, 1349, 1250 cm21. FAB-MS m/z 623 (M111).
Anal. Calcd for C35H38N6O5´0.6H2O: C, 66.36; H, 6.21; N,
13.22%. Found: C, 66.36; H, 6.24; N, 13.27%. [a]2D3268.8
(c 1.02, CHCl3).
(10S,20S,30R)-9-{20,30-Bis[bis(p-methoxyphenyl)phenyl-
methyloxymethyl]cyclobutyl}-N2-(N,N-dimethylamino-
methylene)guanine (ent-12). To a solution of ent-4
(191 mg, 0.35 mmol) in MeOH (5 mL) was added NEt3
(5 mL) and water (1 mL), and the mixture was stirred at
room temperature for 12 h. Then the solvent was removed
in vacuo. The residue was dissolved in MeOH (1 mL), and
(10S,20S,30R)-1-{20,30-Bis[bis(p-methoxyphenyl)phenyl-
methyloxymethyl]cyclobutyl}cytosine (ent-14). To
a
solution of ent-5 (193 mg, 0.44 mmol) in MeOH (5 mL)
was added NEt3 (5 mL) and water (1 mL), and the mixture
was stirred at room temperature for 12 h. The solvent was
removed in vacuo, and the residue was dissolved in dry
pyridine (3 mL). Then under an argon atmosphere added
was bis(p-methoxyphenyl)phenylmethyl chloride (375 mg,
0.88 mmol), and the mixture was stirred at room tempera-
ture for 12 h. The reaction was quenched by addition of
MeOH (2 mL), and the solvent was removed in vacuo.
The residue was diluted with CH2Cl2, and the solution
was washed with saturated aqueous NaHCO3 and brine.
After dried over Na2SO4 the solution was concentrated.
Puri®cation by silica gel ¯ash column chromatography
(AcOEt±hexane, 20:1) gave ent-14 (317 mg, 86%). Mp
132.0±132.58C (CHCl3±hexane). 1H NMR (CDCl3) d
1.70±1.77 (1H, m), 2.01±2.04 (1H, m), 2.51±2.62 (2H,
m), 3.07 (1H, dd, J6.0, 9,6 Hz), 3.15 (1H, dd, J4.8,
9.2 Hz), 3.20 (1H, dd, J8.0, 9.6 Hz), 3.35 (1H, dd,
J5.2, 9.6 Hz), 3.73 (6H, s), 3,76 (6H, s), 4.53 (1H, q,
J8.8 Hz), 5.61 (1H, d, J7.2 Hz), 6.74±6.78 (8H, m),
7.16±7.24 (15H, m), 7.31±7.36 (4H, m), 7.66 (1H, d,
J7.2 Hz). 13C NMR (CDCl3) d 14.3, 30.7, 31.8, 32.2,
44.8, 52.9, 55.28, 55.3, 65.4, 65.7, 85.9, 86.3, 113.0,
113.1, 126.6, 127.7, 128.0, 128.1, 129.9, 135.9, 136.8,
142.8, 144.8, 145.0, 156.3, 158.3, 165.1. IR (KBr) 2931,
1648, 1607, 1508, 1298, 1250, 1175, 1033 cm21. FAB-MS
N,N-dimethylformamide
dimethyl
acetal
(280 mL,
1.40 mmol) was added. The mixture was stirred at room
temperature for 12 h. The solvent was removed in vacuo,
and the residue was dissolved in pyridine (3 mL). Under
an argon atmosphere bis(p-methoxyphenyl)phenylmethyl
chloride (300 mg, 0.88 mmol) was added, and the mixture
was stirred at room temperature for 12 h. The reaction was
quenched by addition of MeOH, and the solvent was
removed in vacuo. The residue was diluted with CH2Cl2,
and the organic solution was washed with saturated aqueous
NaHCO3 and brine. After dried over Na2SO4 the solution
was concentrated. Puri®cation by silica gel ¯ash column
chromatography (AcOEt±hexane, 20: 1) gave ent-12
1
(191 mg, 73%). Mp 125.0±125.58C (CHCl3±hexane). H
NMR (CDCl3) d 2.29±2.32 (2H, m), 2.53±2.56 (1H, m),
2.59 (3H, s), 2.83±2.85 (1H, m), 2.98 (3H, s), 3.11±3.15
(3H, m), 3.32 (1H, dd, J4.4, 9.6 Hz), 3.73 (6H, s), 3.78
(6H, s), 4.90 (1H, q, J8.0 Hz), 6.67±6.73(4H, m), 6.76±
6.79 (4H, m), 7.15±7.25 (14H, m), 7.35±7.42 (4H, d,
J8.4 Hz), 7.72 (1H, s), 8.29 (1H, s), 8.44 (1H, brs). 13C
NMR (CDCl3) d 14.2, 22.7, 30.1, 31.6, 35.1, 40.8, 47.6,
55.15, 55.17, 62.8, 65.2, 85.7, 112.86, 112.9, 126.4, 127.5,