Synthesis and biological activity of nucleoside analogs involving modifications in the carbohydrate ring

Abstract

The synthesis of a variety of nucleoside analogs involving modifications in the carbohydrate ring is described. In particular, 6-substituted purin-9-yl derivatives of 1-oxa-4-thiacyclohexane and 1,4-dioxacyclohexane have been synthesized. A number of 6-chloropurin-9-yl derivatives of substituted 1-oxa-4-thiacyclohexane have also been derived from the parent compounds by way of a Pummerer rearrangement. A route to nucleoside analogs of 1-oxa-4-thiacyclohexane from naturally occurring nucleosides is illustrated for the case of inosine. A route to nucleoside analogs in which the carbohydrate moiety is replaced by an acyclic moiety bearing α,β-unsaturated esters is also illustrated for the case of uridine. The results of biological screening of these analogs and others previously synthesized in our program against leukemia L-1210 cells in vitro are presented; some of these compounds showed marginal antitumor activity. The screening results of selected compounds against the human HeLa cell line in vitro are also presented; none of the compounds that were tested showed significant inhibitory activity of cell growth.