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Liboska, Masojidkova, Rosenberg:
9-[trans-2-(Diisopropylphosphonomethoxy)cyclohexyl]adenine (3b). Diisopropyl phosphonate 3b
was prepared from compound 2b (2.33 g, 10 mmol) as described for the cyclopentane derivative 3a.
Yield 2.30 g (56%) of diisopropyl ester 3b, m.p. 123 °C. UV spectrum: 261 (pH 2), 262 (pH 12).
For C18H30N5O4P (411.4) calculated: 52.55% C, 7.35% H, 17.02% N, 7.53% P; found: 52.44% C,
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7.40% H, 17.03% N, 7.76% P. MS (FAB): 412 (M + H+), 136 (adenine + H+). H NMR spectrum:
0.91 d, 3 H, J(CH,CH3) = 6.1 (CH3); 0.99 d, 3 H, J(CH,CH3) = 6.1 (CH3); 1.01 d, 3 H, J(CH,CH3) = 6.1
(CH3); 1.08 d, 3 H, J(CH,CH3) = 6.1 (CH3); 1.20 m, 1 H, 1.36 m, 2 H, 1.77 m, 1 H, 1.90 m, 1 H,
2.05 m, 1 H, and 2.35 m, 1 H (CCH2); 3.32 dd, 1 H, J(P,CH) = 9.5, J(gem) = 13.7 and 3.68 dd, 1 H,
J(P,CH) = 9.3, J(gem) = 13.7 (PCH2); 4.06 td, 1 H, J(a,e) = 4.4, J(a,a) = 10.5 and 10.7 (OCH); 4.19 dsept,
1 H, J(CH,CH3) = 6.1, J(P,OCH) = 7.6 (POCH); 4.28 dsept, 1 H, J(CH,CH3) = 6.1, J(P,OCH) = 7.6
(POCH); 4.29 m, 1 H (NCH); 7.15 br s, 2 H (NH2); 8.10 s, 1 H and 8.19 s, 1 H (H-2, H-8). 31P NMR
spectrum: 19.59 s (P).
9-[trans-2-(Isopropylphosphonomethoxy)cyclopentyl]adenine (4a). A solution of diester 3a (0.4g,
1 mmol) in aqueous 2 M sodium hydroxide (10 ml) was heated at 80 °C until it disappeared (6 h)
(TLC, H3). Deionization on Dowex 50W X 2 (H+ form) and drying afforded 0.35 g (98%) of amorphous
monoester 4a. UV spectrum: 261 (pH 2), 262 (pH 12). For C14H22N5O4P (355.3) calculated: 47.32% C,
6.24% H, 19.71% N; found: 46.98% C, 6.08% H, 19.52% N. MS (FAB): 356 (M + H+), 314 (M + H+ – C3H7).
1H NMR spectrum: 1.05 d, 3 H, J(CH,CH3) = 6.1 (CH3); 1.07 d, 3 H, J(CH,CH3) = 6.1 (CH3); 1.66–1.72 m,
1 H, 1.75–1.82 m, 1 H, 1.84–1.92 m, 1 H, 2.06 m, 1 H, 2.16 m, 1 H, and 2.22 m, 1 H (CCH2); 3.56 d,
2 H, J(P,CH) = 9.3 (PCH2); 4.36 dsept, 1 H, J(CH,CH3) = 6.1, J(P,OCH) = 8.1 (POCH); 4.42 dt, 1 H,
J = 5.9, 5.9 and 6.8 (OCH); 4.75 td, 1 H, J = 5.9, 8.5 and 8.5 (NCH); 7.52 br s, 2 H (NH2); 8.16 s,
1 H and 8.29 s, 1 H (H-2, H-8).
9-[trans-2-(Isopropylphosphonomethoxy)cyclohexyl]adenine (4b). The title compound was pre-
pared from diester 3b (0.41 g, 1 mmol) in the same manner as the cyclopentane derivative 4a. Yield
of amorphous product 4b was 0.36 g (97%). UV spectrum: 261 (pH 2), 262 (pH 12). For
C15H24N5O4P (369.4) calculated: 48.78% C, 6.55% H, 18.96% N; found: 48.42% C, 6.44% H,
18.92% N. MS (FAB): 370 (M + H+), 328 (M + H+ – C3H7). 1H NMR spectrum: 0.83 d, 3 H,
J(CH,CH3) = 6.1 (CH3); 0.87 d, 3 H, J(CH,CH3) = 6.1 (CH3); 1.36 m, 1 H, 1.45 m, 2 H, 1.88 m, 2 H,
2.04 m, 1 H, 2.12 m, 1 H, and 2.43 m, 1 H (CCH2); 3.26 dd, 1 H, J(P,CH) = 9.0, J(gem) = 13.4 and
3.61 dd, 1 H, J(P,CH) = 9.8, J(gem) = 13.4 (PCH2); 3.92–4.00 m, 2 H (OCH, POCH); 4.44 ddd, 1 H,
J = 4.4, 10.3 and 12.4 (NCH); 8.33 s, 1 H and 8.42 s, 1 H (H-2, H-8).
9-(trans-2-Phosphonomethoxycyclopentyl)adenine (5a). A solution of diester 4a (2 g, 5 mmol) and
trimethylsilyl bromide (4 ml, 30 mmol) in anhydrous acetonitrile (50 ml) was set aside at room tem-
perature for 5 days, then the solvent was evaporated, the residue was dissolved in water and made
alkaline with ammonia to pH 8–9. Chromatography on Dowex 1 X 2 (acetate form) and subsequent
crystallization from water afforded 1.17 g (75%) of phosphonate 5a, m.p. 230 °C. UV spectrum: 261
(pH 2), 262 (pH 12). For C11H16N5O4P (313.3) calculated: 42.18% C, 5.15% H, 22.36% N, 9.89% P;
found: 41.99% C, 6.93% H, 22.11% N, 9.84% P. MS (FAB): 358 (M + 2 Na), 336 (M + Na), 314
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(M + H+), 136 (adenine + H+). H NMR spectrum: 1.80–2.05 m, 4 H, and 2.12–2.48 m, 2 H (CCH2);
3.55 dd, 1 H, J(P,CH) = 9.5, J(gem) = 12.7 and 3.63 dd, 1 H, J(P,CH) = 9.5, J(gem) = 12.7 (PCH2);
4.40 br q, 1 H, J = 5.9 (OCH); 4.75 td, 1 H, J = 6.1, 7.6 and 7.6 (NCH); 8.06 s, 1 H and 8.19 s, 1 H
(H-2, H-8).
9-(trans-2-Phosphonomethoxycyclohexyl)adenine (5b). Compound 5b was prepared from diester
3b (2.05 g, 5 mmol) in the same manner as described for the cyclopentane derivative 5a. Yield of the
product 5b was 1.38 g (82%), m.p. 309 °C. UV spectrum: 261 (pH 2), 262 (pH 12). For
C12H18N5O4P (327.3) calculated: 44.04% C, 5.54% H, 21.40% N, 9.46% P; found: 44.16% C, 5.59% H,
21.63% N, 9.87% P. MS (FAB): 372 (M + 2 Na), 350 (M + Na), 328 (M + H+), 136 (adenine + H+).
1H NMR spectrum: 1.35–1.50 m, 3 H, 1.79–1.90 m, 3 H, 1.99 m, 1 H and 2.45 m, 1 H (CCH2); 3.08 dd,
Collect. Czech. Chem. Commun. (Vol. 61) (1996)