Pyrimidine arabinofuranosyl nucleosides with 5-substituted long, branched and unsaturated chains: synthesis and antiherpes properties

Several procedures have been applied to the preparation of 5-alkyl analogues of araU and araC via condensation of the appropriate 2,4-bis-O-(trimethylsilyl)-5-alkylpyrimidine with 2,3,5-tri-O-benzyl-alpha-D-arabinofuranosyl chloride. The resulting O'-benzylated nucleosides were deblocked with the aid of BF3 . Et2O in C2H5SH. The araC analogues were also prepared by conversions of the corresponding 5-alkyl-araU derivatives. The chloromercuri derivatives of araU and araC, were reacted with allyl chloride in the presence of Li2PdCl4. The resulting 5-allyl derivatives were catalytically reduced to the corresponding 5-propyl analogues. Catalysed condensation of 2,4-bis-O-(trimethylsilyl)-5-vinyluracil with 2,3,5-tri-O-benzyl-alpha-D-arabinosyl chloride, as well as with 1-O-acetyl-2,3,5-tri-O-benzoylarabinofuranose, was carried out under a variety of different conditions. Deblocking of the benzylated nucleosides with various reagents led invariably to addition to the vinyl substituent. In the case of benzoylated nucleosides, deblocking yielded largely the alpha-anomers. The antiherpes activities of the 5-alkyl compounds have been evaluated, as well as the susceptibility of the araC analogues to enzymatic deamination.