H
ELVETICA
CHIMICA
ACTA – Vol. 88 (2005)
3219
J=5.6, HOꢀC(2’)); 4.49–4.55 (m, PhCH2O); 3.75–3.82 (m, HꢀC(1’)); 3.39–3.48 (m, HꢀC(2’), HꢀC(4’));
2.29–2.36 (m, HaꢀC(3’)); 1.97–2.05 (m, HaꢀC(5’), HaꢀC(6’)); 1.21–1.35 (m, HbꢀC(3’), HbꢀC(5’)); 1.04–
1.12 (m, HbꢀC(6’)). 13C-NMR ((D6)DMSO): 152.35 (C(4)); 145.70 (C(6)); 139.18 (C(2)); 136.80, 128.25,
127.40, 127.29 (arom. C); 123.49 (C(5)); 74.99 (C(4’)); 69.57 (PhCH2O); 69.33 (C(2’)); 56.21 (C(1’)); 40.86
(C(3’)); 30.48 (C(5’)); 27.29 (C(6’)). HR-MS: 349.1434 ([M+H]+, C17H22ClN4O2þ ; calc. 349.1431).
(ꢁ)-9-[(1’RS,2’RS,4’RS)-4’-(Benzyloxy)-2’-hydroxycyclohexyl]-6-chloropurine (4). Conc. HCl (1.2 ml) was
added to a soln. of 3 (2 g, 5.73 mmol) in HC(OEt)3 (52 ml). The mixture was stirred at r.t. overnight and con-
centrated to dryness. The residue was dissolved in THF (70 ml), and 0.5
N HCl (70 ml) was added. After 2 h
at r.t., the soln. was neutralized with 1 NaOH and diluted with CH2Cl2. The phases were separated, and the
N
org. phase was dried (Na2SO4), filtered, and concentrated to dryness. The residue was purified by FC (hex-
1
ane/AcOEt 50 :50 to 10 :90) to give 1.56 g (76%) of 4. White solid. H-NMR ((D6)DMSO): 8.75 (s, HꢀC(2));
8.72 (s, HꢀC(8)); 7.28–7.37 (m, 5 arom. H); 5.09 (d, J=5.6, HOꢀC(2’)); 4.55–4.61 (m, PhCH2O); 4.28–4.35
(m, HꢀC(1’)); 4.05–4.12 (m, HꢀC(2’)); 3.52–3.60 (m, HꢀC(4’)); 2.38–2.45 (m, HaꢀC(3’)); 2.10–2.18 (m,
HaꢀC(5’), HaꢀC(6’)); 1.96–2.02 (m, HbꢀC(6’)); 1.36–1.46 (m, HbꢀC(3’), HbꢀC(5’)). 13C-NMR
((D6)DMSO): 152.24 (C(2)); 151.05 (C(6)); 148.90 (C(4)); 146.93 (C(8)); 139.02 (arom. C); 131.30 (C(5));
128.29, 127.46, 127.36 (arom. C); 74.19 (C(4’)); 69.35 (PhCH2O); 68.00 (C(2’)); 61.39 (C(1’)); 40.60 (C(3’));
30.56 (C(5’)); 26.54 (C(6’)). HR-MS: 359.1274 ([M+H]+, C18H20ClN4O2þ ; calc. 359.1275).
(ꢁ)-9-[(1’RS,2’RS,4’RS)-4’-(Benzyloxy)-2’-hydroxycyclohexyl]adenine (5). A suspension of 4 (2 g, 5.6
mmol) in a MeOH soln. sat. with NH3 (50 ml) was heated in a sealed tube at 1008 overnight. NH3 and
MeOH were evaporated. The residue was purified by CC (CH2Cl2/MeOH 98 :2 to 90 :10) to afford 1.65 g
(84%) of 5. White powder. 1H-NMR ((D6)DMSO): 8.11 (s, HꢀC(2), HꢀC(8)); 7.28–7.38 (m, 5 arom. H);
7.12 (br. s, NH2); 4.99 (d, J=5.6, HOꢀC(2’)); 4.55, 4.57 (AB, J=12.2, PhCH2O); 4.05–4.16 (m, HꢀC(1’), Hꢀ
C(2’)); 3.49–3.56 (m, HꢀC(4’)); 2.36–2.41 (m, HaꢀC(3’)); 2.02–2.15 (m, HaꢀC(5’), HaꢀC(6’)); 1.87–1.91
(m, HbꢀC(6’)); 1.32–1.42 (m, HbꢀC(3’), HbꢀC(5’)). 13C-NMR ((D6)DMSO): 156.01 (C(6)); 151.95 (C(2));
149.76 (C(4)); 140.39 (C(8)); 139.09, 128.32, 127.48, 127.38 (arom. C); 119.28 (C(5)); 74.37 (C(4’)); 69.36
(PhCH2O); 67.81 (C(2’)); 60.40 (C(1’)); 41.02 (C(3’)); 30.72 (C(5’)); 27.11 (C(6’)). HR-MS: 340.1170
([M+H]+, C18H22N5Oþ2 ; calc. 340.1173).
(ꢁ)-9-{(1’RS,2’RS,4’RS)-4’-(Benzyloxy)-2’-[(tert-butyl)dimethylsilyloxy]cyclohexyl}adenine (6). To a pre-
chilled (08) soln. of 5 (947 mg, 2.79 mmol) and 1H-imidazole (1.08 g, 15.9 mmol) in DMF (28 ml) was added
TBDMSCl (1.36 g, 9.02 mmol). After one night at r.t., Et2O was added, and the mixture was washed with sat.
aq. NaHCO3 soln., 1N HCl, and H2O. The org. phase was dried (Na2SO4), filtered, and concentrated to dryness.
The residue was purified by CC (CH2Cl2/MeOH 100 :0 to 94 :6) to give 1.02 g (81%) of 6. White solid. 1H-NMR
((D6)DMSO): 8.10 (s, HꢀC(2)); 8.09 (s, HꢀC(8)); 7.28–7.36 (m, 5 arom. H); 7.08 (br. s, NH2); 4.54, 4.59 (AB,
J=12.1, PhCH2O); 4.16–4.26 (m, HꢀC(1’), HꢀC(2’)); 3.54–3.61 (m, HꢀC(4’)); 2.27–2.34 (m, HaꢀC(3’), Haꢀ
C(6’)); 2.13–2.20 (m, HaꢀC(5’)); 1.84–1.91 (m, HbꢀC(6’)); 1.34–1.45 (m, HbꢀC(3’), HbꢀC(5’)); 0.55 (s, t-Bu);
ꢀ0.18 (s, MeSi); ꢀ0.66 (s, MeSi). 13C-NMR ((D6)DMSO): 156.03 (C(6)); 151.87 (C(2)); 149.66 (C(4)); 140.55
(C(8)); 139.05, 128.29, 127.51, 127.39 (arom. C); 119.46 (C(5)); 74.24 (C(4’)); 70.04 (PhCH2O); 69.57 (C(2’));
60.43 (C(1’)); 41.38 (C(3’)); 30.55 (C(5’)); 26.19 (C(6’)); 25.32 (Me3C); 17.19 (Me3C); ꢀ4.73, ꢀ6.00 (Me2Si).
HR-MS: 454.2639 ([M+H]+, C24H36N5O2Si+; calc. 454.2638).
(ꢁ)-9-{(1’RS,2’RS,4’RS)-2’-[(tert-Butyl)dimethylsilyloxy]-4’-hydroxycyclohexyl}adenine (7). A mixture of 6
(778 mg, 1.72 mmol), NH4OCOH (922 mg, 14.6 mmol), and Pd/C (1g) in MeOH (42 ml) was refluxed for 5 h.
NH4OCOH (461 mg, 7.31 mmol) was added again, and heating was continued for 2 h. After cooling to r.t.,
the mixture was filtered through Celite, and the catalyst was washed with MeOH. The filtrate was concentrated
to dryness, and the residue was purified by CC (CH2Cl2/MeOH 98 :2 to 90 :10) to yield 603 mg (96%) of 7. White
foam. 1H-NMR ((D6)DMSO): 8.11 (s, HꢀC(2)); 8.09 (s, HꢀC(8)); 7.06 (br. s, NH2); 4.79 (d, J=4.6, HOꢀC(4’));
4.17–4.23 (m, HꢀC(1’); 4.10–4.17 (m, HꢀC(2’)); 3.61–3.69 (m, HꢀC(4’)); 2.29–2.34 (m, HaꢀC(6’)); 2.14–2.21
(m, HaꢀC(3’)); 1.89–1.96 (m, HaꢀC(5’)); 1.78–1.86 (m, HbꢀC(6’)); 1.29–1.40 (m, HbꢀC(3’), HbꢀC(5’)); 0.55 (s,
Me3C); ꢀ0.18 (s, MeSi); ꢀ0.65 (s, MeSi). 13C-NMR ((D6)DMSO): 156.00 (C(6)); 151.86 (C(2)); 149.64 (C(4));
140.51 (C(8)); 119.42 (C(5)); 70.20 (C(4’)); 66.46 (C(2’)); 60.39 (C(1’)); 44.60 (C(3’)); 33.98 (C(5’)); 26.50
(C(6’)); 25.31 (Me3C); 17.20 (Me3C); ꢀ4.76, ꢀ5.95 (Me2Si). HR-MS: 364.2166 ([M+H]+, C17H30N5O2Si+;
calc. 364.2169).
(ꢁ)-N6-Benzoyl-9-{(1’RS,2’RS,4’RS)-2’-[(tert-butyl)dimethylsilyloxy]-4’-hydroxycyclohexyl}adenine (8). To
a prechilled (08) soln. of 7 (552 mg, 1.52 mmol) in pyridine (8 ml) was added Me3SiCl (1 ml, 7.82 mmol). After
1 h at 08, BzCl (900 ml, 7.75 mmol) was added, and the mixture was stirred at r.t. overnight. After cooling to 08,
H2O (2 ml) was added. The mixture was stirred for 5 min, and 25% aq. NH4OH soln. (4 ml) was added. After
15 min at 08, the solvents were evaporated. The residue was dissolved in MeOH (3 ml) and 25% aq. NH4OH