Enantiomeric Derivatives of Purine and Pyrimidine Bases
1401
added in one portion. The mixture was then heated for 24 h at 110 °C under exclusion of moisture
and taken down to dryness. The residue was extracted with boiling chloroform (300 ml total), filtered
and the filtrate evaporated. The residue was chromatographed on a column of silica gel (300 ml) in
chloroform. Crystallization from ethyl acetate–light petroleum gave bis(2-propyl) (R)-9-(2-phosphono-
methoxypropyl)-3-deazaadenine (XIc) (1.07 g, 32%), m.p. 122 °C. For C16H27N4O4P (370.5) calcu-
lated: 51.87% C, 7.35% H, 15.13% N, 8.38% P; found: 52.03% C, 7.69% H, 15.15% N, 8.59% P.
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UV spectrum (pH 2): λmax 262 (ε 16 500). H NMR spectrum ((CD3)2SO): 7.99 s, 1 H (H-8); 7.66 d,
1 H, J(2,3) = 5.9 (H-2); 6.85 d, 1 H, J(2,3) = 5.9 (H-3); 6.16 br s, 2 H (NH2); 4.50 m, 2 H, J(P,OCH) = 7.3,
J(CH,CH3) = 6.1 (POCH); 4.29 dd, 1 H, J(1′a,2′) = 4.2, J(gem) = 14.6 (H-1′a); 4.16 dd, 1 H, J(1′b,2′) = 6.1,
J(gem) = 14.6 (H-1′b); 3.90 m, 1 H (H-2′); 3.78 dd, 1 H, J(P,CHa) = 9.1, J(gem) = 13.9 (P-CHa);
3.67 dd, 1 H, J(P,CHb) = 9.5, J(gem) = 13.9 (P-CHb); 1.19 d, 3 H, and 1.16 d, 6 H, and 1.13 d, 3 H,
and 1.07 d, 3 H, J = 6.1 (5 × CH3).
Bis(2-propyl) (R)-9-(2-Phosphonomethoxypropyl)-2-amino-6-chloropurine (XId)
Sodium hydride (60% dispersion; 1.4 g, 35 mmol) was added to a stirred solution of 2-amino-6-
chloropurine (5.94 g, 35 mmol) in dimethylformamide (60 ml) and, after stirring at ambient tempera-
ture for 1 h, (R)-2-[bis(2-propyl)phosphonylmethoxy]propyl p-toluenesulfonate (X) (12.2 g, 30 mmol)
in dimethylformamide (20 ml) was added. The mixture was stirred at 80 °C for 10 h and evaporated
in vacuo. The residue was extracted with boiling chloroform (300 ml), filtered and the filtrate was
evaporated in vacuo. Column chromatography on silica gel (chloroform–methanol, 95 : 5) and crys-
tallization from ethyl acetate (light petroleum added to turbidity) gave bis(2-propyl) (R)-9-(2-phos-
phonomethoxypropyl)-2-amino-6-chloropurine (XId) (10.7 g, 88%), m.p. 134–135 °C. [α]D –24.3° (c 1,
DMF), RF 0.55 (S2). For C15H25ClN5O4P (405.9) calculated: 44.38% C, 6.21% H, 8.74% Cl, 17.26% N,
7.65% P; found: 44.45% C, 6.35% H, 8.52% Cl, 16.88% N, 7.74% P. 1H NMR spectrum
((CD3)2SO): 8.03 s, 1 H (H-8); 6.89 s, 2 H (NH2); 4.50 m, 2 H, J(P,OCH) = 7.6 (POCH); 4.16 dd,
1 H, J(1′a,2′) = 4.4, J(gem) = 14.4 (H-1′a); 4.05 dd, 1 H, J(1′b,2′) = 7.3, J(gem) = 14.4 (H-1′b); 3.94 m,
1 H (H-2′); 3.79 dd, 1 H, J(P,CHa) = 9.0, J(gem) = 13.7 (P-CHa); 3.67 dd, 1 H, J(P,CHb) = 9.5,
J(gem) = 13.7 (P-CHb); 1.19 d, 3 H, and 1.14 d, 6 H, J = 6.3, and 1.11 d, 3 H, J = 6.1, and 1.09 d,
3 H, J = 6.3 (5 × CH3).
Further elution gave 1.15 g of crude compound XXIV, m.p. 139–140 °C (ethyl acetate–light petroleum),
RF 0.47 (S2). For C15H25ClN5O4P (405.9) calculated: 44.38% C, 6.21% H, 8.74% Cl, 17.26% N,
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7.65% P; found: 44.45% C, 6.37% H, 8.90% Cl, 17.17% N, 7.34% P. H NMR spectrum ((CD3)2SO)
(major component, about 70%): 8.24 s, 1 H (H-8); 6.61 s, 2 H (NH2); 4.45 m, 2 H (POCH); 4.38 dd,
1 H, J(1′a,2′) = 3.2, J(gem) = 14.7 (H-1′a); 4.28 dd, 1 H, J(1′b,2′) = 9.2, J(gem) = 14.7 (H-1′b); 3.92 m,
1 H (H-2′); 3.75 dd, 1 H, J(P,CHa) = 9.0, J(gem) = 13.9 (P-CHa); 3.59 dd, 1 H, J(P,CHb) = 9.2,
J(gem) = 13.9 (P-CHb); 1.17 d, 3 H, and 1.14 d, 6 H, and 1.11 d, 3 H, and 1.08 d, 3 H, J(CH3,CH)
= 6.1 (5 × CH3).
Bis(2-propyl) (R)-9-(2-Phosphonomethoxypropyl)guanine (XIe)
A mixture of compound XId (2.02 g, 5 mmol), potassium carbonate (0.70 g), DABCO (0.65 g) and
water (60 ml) was refluxed for 2 h, cooled, acidified by addition of Dowex 50 X 8 (H+ form), made
alkaline with triethylamine, filtered, and the resin was washed thoroughly with methanol. The filtrate
was evaporated in vacuo to dryness and the residue was purified by preparative TLC on a silica gel
plate (see above) in chloroform–methanol (85 : 15). The band of the product was eluted with methanol,
evaporated and crystallized from ethanol (ether added to turbidity). Yield 1.35 g (70%), m.p. 208 °C,
[α]D –8.5° (c 1, DMF). For C15H26N5O5P (387.4) calculated: 46.51% C, 6.77% H, 18.08% N, 8.00% P;
found: 46.70% C, 6.92% H, 17.77% N, 7.68% P. 1H NMR spectrum ((CD3)2SO): 10.58 brs, 1 H
Collect. Czech. Chem. Commun. (Vol. 60) (1995)