Synthesis and anti-HIV Study of Novel Acyclic Guanine Derivatives

Abstract

This paper reports a new method for synthesizing an acyclic version of 6 '-methylene and 6 '(alpha)-methylated carbovir analogues. The introduction of a methylene group to the requisite 6 '-position was carried out employing a Mannich type reaction using Eshenmoser's salt (methylene-N,N-dimethylammonium iodide). Carbonyl enolate alkylation (LiHMDS, CH3I) was used to introduce a methyl group to the 6 '(alpha)-position. The guanine analogues were successfully synthesized from the bromide compound 8 and 14 via a SN2 type reaction and deprotection. When the synthesized compounds 11 and 17 were tested against HIV-1, they showed toxicity that was not related to any anti-HIV activity.