1402
Janeba, Holý, Masojídková:
6-Am in o-9-[(RS)-(2,2-dim eth yl-1,3-dioxolan -4-yl)m eth yl]-7H-purin -8(9H)-th ion e (9)
A m ixture of th e 8-brom o derivative10 8 (2.5 g, 7.6 m m ol) an d th iourea (4.6 g, 60 m m ol), in
eth an ol (60 m l) was refluxed for 6 h , an d evaporated in vacuo. Th e residue was suspen ded in
h ot ch loroform (100 m l), th iourea was filtered off an d wash ed with h ot ch loroform (250 m l).
Th e ch loroform solution was taken down in vacuo. Ch rom atograph y of th e residue in ch lo-
roform on a colum n of silica gel (60 g) with ch loroform –m eth an ol gradien t, followed by
crystallization from eth yl acetate afforded 0.55 g (26%) of com poun d 9. Wh ite crystals, m .p.
216 °C, RF 0.38 (S2). FAB MS, m/z (rel.%): 282 (100) [M + H]. 1H NMR (DMSO-d6): 1.21 (s, 3 H,
CH3); 1.40 (s, 3 H, CH3); 3.95 (d, 2 H, J(3′,2′) = 5.3, H-3′); 4.14 (dd, 1 H, J(1′b,2′) = 6.6,
J(gem ) = 13.5, H-1′b); 4.26 (dd, 1 H, J(1′a,2′) = 6.5, J(gem ) = 13.5, H-1′a); 4.63 (tt, 1 H, J = 5.3
an d 6.5, H-2′); 6.86 (brs, 2 H, NH2); 8.15 (s, 1 H, H-2); 12.38 (brs, 1 H, NH). 13C NMR
(DMSO-d6): 25.39 (CH3); 27.02 (CH3); 45.38 (C-1′); 66.78 (C-3′); 72.25 (C-2′); 107.02 (C-5);
109.04 (C-ipso); 147.81 (C-6); 149.56 (C-4); 152.71 (C-2); 166.97 (C-8). For C11H15N5O2S
(281.3) calculated: 46.96% C, 5.37% H, 24.89% N, 11.40% S; foun d: 46.90% C, 5.47% H,
24.63% N, 11.25% S. UV, λm ax (εm ax): (MeOH) 307 (24 700), 233 (14 900).
Reaction of Com poun d 9 with (S)-[(Trityloxy)m eth yl]oxiran e
Method A: A m ixture of com poun d
9 (0.5 g, 1.8 m m ol), DMF (15 m l), (S)-[(trityl-
oxy)m eth yl]oxiran e (0.6 g, 1.9 m m ol) an d caesium carbon ate (0.12 g, 0.4 m m ol) was stirred
at 110 °C for 3 h . Th e sam e workup as described for alkylation of com poun d 1 afforded
0.42 g (40%) of com poun d 10 an d 0.2 g (42%) of com poun d 11.
Method B: A m ixture of com poun d 9 (0.5 g, 1.8 m m ol), DMF (20 m l) an d NaH (72 m g of
60% dispersion , 1.8 m m ol) was stirred at 100 °C for 0.5 h . (S)-[(Trityloxy)m eth yl]oxiran e
(0.6 g, 1.9 m m ol) was added an d th e m ixture was stirred at 100 °C for an oth er 2.5 h . Th e
sam e workup as in m eth od A afforded 0.3 g (64%) of com poun d 11.
9-[((RS)-2,2-Dimethyl-1,3-dioxolan-4-yl)methyl]-8-{[(R)-2-hydroxy-3-(trityloxy)propyl]sulfanyl}-
adenine (10). Wh ite crystals, m .p. 94–95 °C, RF 0.42 (S1). FAB MS, m/z (rel.%): 598 (25) [M + H];
243 (100) [Tr]. 1H NMR (DMSO-d6): 1.19 (s, 3 H, CH3); 1.26 an d 1.265 (2 × s, 3 H, CH3);
2.935 an d 2.94 (2 × dd, 1 H, J(3′′b,2′′) = 5.4, J(gem ) = 9.3, H-3′′b); 3.02 (brdd, 1 H, J(3′′a,2′′) =
5.5, J(gem ) = 9.3, H-3′′a); 3.425 an d 3.44 (2 × dd, 1 H, J(1′′b,2′′) = 5.5, J(gem ) = 13.2, H-1′′b);
3.51 an d 3.52 (2 × dd, 1 H, J(1′′a,2′′) = 5.2, J(gem ) = 13.2, H-1′′a); 3.815 an d 3.82 (2 × dd, 1 H,
J(3′b,2′) = 5.0, J(gem ) = 8.7, H-3′b); 3.95 (brsext, 1 H, J = 5.5, H-2′′); 3.987 an d 3.99 (2 × dd,
1 H, J(3′a,2′) = 6.6, J(gem ) = 8.7, H-3′a); 4.02 (dd, 0.5 H, J(1′b,2′) = 6.5, J(gem ) = 14.5, H-1′b);
4.05 (d, 1 H, J(1′,2′) = 5.7, H-1′); 4.08 (dd, 0.5 H, J(1′a,2′) = 5.1, J(gem ) = 14.5, H-1′a); 4.42
(pen t, 1 H, J = 5.7, H-2′); 5.38 (d, 1 H, J(OH,2′′) = 5.4, OH-2′′); 7.06 (brs, 2 H, NH2); 7.23 (t,
3 H, arom . H); 7.29 (t, 6 H, arom . H); 7.36 (d, 6 H, arom . H); 8.09 (s, 1 H, H-2). 13C NMR
(DMSO-d6): 25.19 (CH3); 26.65 (CH3); 37.24 (C-1′′); 45.67 (C-1′); 66.360 an d 66.365 (C-3′
an d C-3′′); 68.63 (C-2′′); 73.35 (C-2′); 86.05 (C-Ph ); 109.18 (C-i-Pr); 118.90 (C-5); 127.12 (3 C,
C-arom .); 127.97 (6 C, C-arom .); 128.44 (6 C, C-arom .); 143.89 (3 C, C-arom .); 149.06 (C-8);
151.54 (C-4); 151.90 (C-2); 154.28 (C-6).
6-Amino-9-[(RS)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-7H-purin-8(9H)-one (11). Wh ite crys-
tals, m .p. 229 °C, RF 0.18 (S1). FAB MS, m/z (rel.%): 266 (100) [M + H]. 1H NMR (DMSO-d6):
1.21 (s, 3 H, CH3); 1.32 (s, 3 H, CH3); 3.75 (dd, 1 H, J(1′b,2′) = 6.3, J(gem ) = 13.9, H-1′b);
3.84 (dd, 1 H, J(3′b,2′) = 4.8, J(gem ) = 8.7, H-3′b); 3.85 (dd, 1 H, J(1′a,2′) = 6.3, J(gem ) = 13.9,
H-1′a); 3.97 (dd, 1 H, J(3′a,2′) = 6.2, J(gem ) = 8.7, H-3′a); 4.42 (qd, 1 H, J(2′,3′b) = 4.8,
J(2′,3′a) = J(2′,1′) = 6.3, H-2′); 6.43 (brs, 2 H, NH2); 8.02 (s, 1 H, H-2); 10.18 (brs, 1 H, NH).
Collect. Czech. Chem. Commun. (Vol. 66) (2001)