Synthesis of acyclic nucleotide analogues derived from N-3-substituted isoguanine

Reaction of 9-benzyl-6-{[(dimethylamino)methylidene]amino}purin-2(3H)-one ( 7) with ethylene carbonate gave a mixture of 9-benzyl-2-(2-hydroxyethoxy)pu rin-6-amine (10) and 2-amino-9-benzyl-3-(2-hydroxyethyl)purin-2(3H)-one (11 ). This mixture reacted with diisopropyl (tosyloxymethyl)phosphonate in the presence of NaH followed by catalytic hy drogenation and bromotrimethylsil ane treatment to afford isomeric 6-amino-3-[2-(phosphonomethoxy)ethyl]purin -2(3H)-one (3) and 2-[2-(phosphonomethoxy)ethoxy]purin-6-amine (15). Simila r treatment of compound 7 with tritylglycidol gave two isomeric 2-hydroxy-3 -(trityloxy)propyl derivatives 18, 20 which were subsequently condensed wit h diisopropyl (tosyloxymethyl)phosphonate to afford protected diester inter mediates 21 and 22; these compounds were transformed by hydrogenolysis and ester cleavage with bromotrimethlylsilane to the isomeric 6-amino-3-[3-hydr oxy-2-(phosphonomethoxy)propyl]-purin-2(3H)-one (2) and 2-[3-hydroxy-2-(pho sphonomethoxy)propoxy]purin-6-amine (24). None of the free phosphonates 2, 3, 15 or 24 exhibited any antiviral or cytostatic activity.