Y. Kitade et al. / Tetrahedron 58 (2002) 1271±1277
1275
0.0043 mmol) was added to the solution and the mixture
was re¯uxed at 908C for 10 min under Ar atmosphere.
Trimethylaluminium (0.98 M n-hexane solution) (0.7 mL)
was slowly dropped to the solution. The reaction mixture
was stirred at 908C for 2 h under Ar atmosphere and
quenched by methanol at 08C. The suspension was evapo-
rated. Chloroform (5 mL) was added to the residue and
washed with distilled water (5 mL). After the organic
layer was dried on sodium sulfate and ®ltrated, the ®ltrate
was evaporated. Methanol (10 mL) and 1 M ammonium
chloride solution (5 mL) were added to the residue and
the mixture was stirred at 908C for 3.5 h. The reaction
mixture was evaporated and the residue was puri®ed by
silica-gel column chromatography eluting with chloro-
form±methanol (10:1). Fractions were evaporated under
reduced pressure and the residue was triturated with
1-propanol to give 8-methylnoraristeromycin (8) (46 mg,
(3.6 mL) and H2O (0.4 mL) was treated with 2% Osmium
tetraoxide solution (72 mL) in the presence of 4-methyl-
morpholine N-oxide (40 mg, 0.33 mmol) and stirred at
room temperature for 5 h. The reaction mixture was evapo-
rated under reduced pressure and the residue was puri®ed by
silica-gel column chromatography eluting with chloro-
form±methanol (10:1). Compound 10 was obtained
(38 mg, 99%) as a solid: mp123±124 8C; FTIR (KBr)
1
3330, 3223, 1634, 1619, 1472 cm21; H NMR (400 MHz,
DMSO-d6) d 1.69 (m, 1H, H-50), 2.56 (m, 1H, H-50), 3.73
(br s, 1H, H-30), 3.86 (m, 1H, H-40), 4.43 (m, 1H, H-20), 4.62
(m, 1H, 1-H0), 4.88 (d, J3.6 Hz, 1H, OH-30), 5.03 (d, J
4.8 Hz, 1H, OH-20), 5.16 (d, J4.0 Hz, 1H, OH-40), 6.86 (s,
2H, C2±NH2), 8.18 (s, 1H, H-8); EI MS (m/z, relative
intensity) 287 (6), 285 (M1, 18), 196 (53), 170 (100), 134
(74); Anal. calcd for C10H12ClN5O3´3/5MeOH´3/5H2O: C,
40.32; H, 4.98; N, 22.18. Found: C, 40.49; H, 4.85; N, 22.00.
22
55%) as a solid: mp250 8C (dec.); [a]D 243.78 (c 1.04,
DMF); FTIR (KBr) 3451, 3293, 1644, 1343, 1089 cm21; 1H
NMR (400 MHz, DMSO-d6) d 2.11 (m, 1H, H-50), 2.47 (m,
1H, H-50), 2.49 (s, 3H, CH3), 3.71 (s, 1H, H-30), 3.84 (m,
1H, H-40), 4.52 (m, 1H, H-10), 4.61 (m, 1H, H-20), 4.85 (d,
J4.0 Hz, 1H, OH-30), 4.93 (d, J6.8 Hz, 1H, OH-20), 5.80
(d, J6.4 Hz, 1H, OH-40), 7.10 (s, 2H, C6±NH2), 8.02 (s,
1H, H-2); 13C NMR (100 MHz, DMSO-d6) d 14.21, 34.18,
58.94, 74.05, 74.21, 76.70, 118.00, 149.33, 149.56, 150.81,
155.22; EI MS (m/z, relative intensity) 265 (M1, 6), 204 (6),
176 (64), 149 (100), 122 (28); HRMS (EI) Calcd for
C11H15N5O3 265.1175. Found 265.1182. Anal. calcd for
C11H15N5O3´3/5PrOH: C, 51.02; H, 6.62; N, 23.24. Found:
C, 51.38; H, 6.26; N, 23.28.
3.1.8. 9-[(10R,20S,30R,40S)-20,30,40-Trihydroxycyclopen-
tan-10-yl]-9-H-2-aminoadenine11 (2-aminonoraristero-
mycin, 11). Compound 10 (21 mg, 0.075 mmol) was
treated with methanolic ammonia (35 mL) and heated in a
sealed tube at 1008C for 24 h. The solvent was evaporated
and the residue was puri®ed by silica-gel column chroma-
tography eluting with chloroform±methanol (10:1). Frac-
tions were evaporated under reduced pressure and the
residue was triturated with EtOAc and ethanol to give
2-aminonoraristeromycin (11) (12 mg, 62%) as a solid:
22
mp116±118 8C; [a]D 261.48 (c 0.22, DMF); FTIR
(KBr) 3324, 3140, 1669, 1597, 1418 cm21 1H NMR
;
(400 MHz, DMSO-d6) d 1.66 (br s, 1H, H-50), 2.55 (m,
1H, H-50), 3.72 (br s, 1H, H-30), 3.85 (br s, 1H, H-40),
4.42 (br s, 1H, H-20), 4.50 (m, 1H, H-10), 4.78 (br s, 1H,
OH-30), 5.02 (br s, 1H, OH-20), 5.41 (br s, 1H, OH-40), 5.81
and 6.79 (br s, each 2H, C2±NH2 and C6±NH2), 7.76 (s, 1H,
H-8); 13C NMR (100 MHz, DMSO-d6) d 37.00, 57.57,
73.64, 75.68, 77.02, 113.50, 136.47, 151.77, 156.23,
159.98; EI MS (m/z, relative intensity) 266 (M1, 17), 177
(55), 150 (100), 108 (33); HRMS (EI) Calcd for C10H14N6O3
266.1127. Found 266.1130. Anal. calcd for C10H14N6O3´
EtOAc´2/3EtOH: C, 47.83; H, 6.81; N, 21.82. Found: C,
47.57; H, 7.19; N, 21.79.
3.1.6. 9-[(10R,40S)-40-Hydroxy-20-cyclopenten-10-yl]-9-
H-2-amino-6-chloropurine (9). This compound was
prepared by the analogous method for the preparation of
noraristeromycin (3). A solution of 2-amino-6-chloropurine
(368 mg, 2.2 mmol) and 60% NaH (84 mg, 2.1 mmol) in
DMSO (5 mL) was stirred at room temperature for 0.5 h
under Ar atmosphere. The reaction mixture was added to
a solution of compound 4 (258 mg, 1.8 mmol), triphenyl-
phosphine (84 mg, 0.32 mmol) and tetrakis(triphenyl-
phosphine)palladium(0) (260 mg, 0.15 mmol) in dry THF
in the dark and stirred at 558C for 2 days under Ar atmos-
phere. The reaction mixture was evaporated under reduced
pressure. Chloroform was added to the residue and the
insoluble matter was removed by ®ltration. The ®ltrate
was evaporated under reduced pressure and puri®ed by
silica-gel column chromatography eluting with chloro-
form±methanol (60:1). Fractions were evaporated under
reduced pressure and the residue was triturated with 1-buta-
nol to give compound 9 (180 mg, 40%) as a solid: mp159±
1608C; FTIR (KBr) 3206, 1636, 1570, 1408, 1200 cm21; 1H
NMR (400 MHz, CDCl3) d 2.05 (d, J14.8 Hz, 1H, H-50),
2.87 (m, 1H, H-50), 4.77 (d, J5.2 Hz, 1H, H-40), 5.17 (d,
J8.8 Hz, 1H, H-10), 5.25 (s, 2H, C2±NH2), 5.77 (s, 1H,
H-20), 6.24 (s, 1H, H-30), 8.02 (s, 1H, H-8); EI MS (m/z,
relative intensity) 253 (6), 251 (M1, 20), 222 (22), 169 (94),
134 (100); Anal. calcd for C10H10ClN5O´1/4BuOH: C,
48.90; H, 4.66; N, 25.92. Found: C, 49.16; H, 4.34; N, 26.17.
3.1.9. 9-[(10R,20S,30R,40S)-20,30,40-Triacetoxycyclopen-
tan-10-yl]-9-H-2-amino-6-chloropurine (12). The solution
of compound 10 (130 mg, 0.49 mmol) in DMF (12 mL) was
treated with acetic anhydride (194 mL) in the presence of
pyridine (9 mL) and stirred at room temperature for 20 h.
The solvent was evaporated under reduced pressure and the
residue was puri®ed by silica-gel column chromatography
eluting with chloroform±methanol (50:1). Compound 12
was obtained (132 mg, 70%) as a solid: mp60±62 8C;
1
FTIR (KBr) 1745, 1611, 1565, 1374, 1231 cm21; H NMR
(400 MHz, CDCl3) d 1.92 (s, 3H, OCOCH3), 2.07 (s, 6H,
OCOCH3), 2.24 (m, 1H, H-50), 2.85 (m, 1H, H-50), 4.82 (m,
1H, H-30), 5.13 (m, 1H, H-40), 5.43±5.48 (m, 3H, H-30 and
C2±NH2), 5.73 (dd, J8.0 and 5.6 Hz, 1H, H-20), 7.77 (s,
1H, H-8); 13C NMR (100 MHz, CDCl3) d 20.30, 20.48,
20.78, 32.59, 56.12, 73.27, 73.41, 73.50, 125.47, 140.93,
151.41, 153.48, 158.91, 169.21, 169.52, 169.70; EI MS
(m/z, relative intensity) 413 (8), 411 (M1, 30), 353 (38),
250 (100), 170 (98); HRMS (EI) Calcd for C16H18ClN5O6
411.0946. Found 411.0935.
3.1.7.
9-[(10R,20S,30R,40S)-20,30,40-Trihydroxycyclo-
pentan-10-yl]-9-H-2-amino-6-chloropurine11 (10). The
solution of compound 9 (33 mg, 0.13 mmol) in THF