Studies on 7-(3,5-dideoxy-2-C-methoxycarbonyl-β-L-pentofuranosyl)-theophyllines. Configuration at the branch point and biological activity

Abstract

The structures of the recently prepared ‘saccharinic acid’ nucleosides have been established by chemical and spectroscopic means. Reduction of 7-[3,5-dideoxy-2-C-methoxycarbonyl-β-L-erythro-(and threo-)pentofuranosyl]theophylline (1A and 1B) with sodium borohydride gave 7-[3,5-dideoxy-2-C-hydroxymethyl-β-L-erythro-(and threo-)pentofuranosyl]theophylline (2A and B). Selective tosylation of (2A and B) produced the 2′-tosyloxymethyl derivatives (3A and B). On heating in dioxan (3A) gave the cyclonucleoside (4A), indicating the erythro-structure of (2A) and consequently the threo-structure of (2B). The erythro-isomer showed significant growth inhibitory activity against KB cells, whereas the threo-hydroxymethyl derivative was inactive under the same conditions.