SYNTHESIS OF C-6 PYRIMIDINE ACYCLIC NUCLEOSIDE ANALOGS AS POTENTIAL ANTIVIRAL AGENTS

A number of pyrimidine acyclic nucleosides in which the acyclic moiety is attached to the C-6 position rather than N-1 of the pyrimidine rin g have been prepared. This was accomplished via treatment of lithiated 2,4-methoxy-5,6-dimethylpyrimidine, or, 2,4-dimethoxy-6-methylpyrimid ine with 1,3-bis-(benzyloxy)-2-propanone, benzyl chloromethyl ether or oxirane, respectively, to give the corresponding key intermediates zy loxy-2-(benzyloxy)methyl-2-hydroxypropyl-2,4- dimethoxy-5-methylpyr imidine (2a), y)methyl-2-hydroxypropyl-2,4-dimethoxypyrimidine (2b), 2-benzyloxyethyl)-2,4-dimethoxy-5-methylpyrimidine (3), and 4-dimetho xy-6-(3-hydroxypropyl)-5-methylpyrimidine (4a). After acidic hydrolysi s, followed by debenzylation with boron trichloride these key intermed iates were converted to the target C-6 pyrimidine acyclic derivatives. Compounds 6-8b, 11-13, 15, 16, 20, 22, 26, and 29-32 were evaluated f or activity against herpes viruses and human immunodeficiency virus. N one of the compounds were active against the viruses nor were they cyt otoxic at the highest concentration tested.