Synthesis of N 4 -β-D-glycoside cytosines and sugar N 4 -acetylcytosin-1-ylmethylhydrazones as antiviral agents

Abstract

Reaction of monosaccharide aldoses with cytosine (1) gave stereoselectively β-N-glycosides 2a–d, which were treated with acetic anhydride in pyridine to afford the corresponding acetylated derivatives 3a–d. N⁴-Acetylcytosine (4) was synthesised and treated with ethyl chloroacetate to give 1-(ethoxycarbonylmethyl)-N⁴-acetylcytosine (5). Hydrolysis of the latter ester with hydrazine hydrate afforded the hydrazide derivative 6. Condensation of the hydrazide with monosaccharide aldoses gave the corresponding sugar hydrazones 7a–f. Acetylation of the hydrazones afforded the per-O-acetyl derivatives 8a–f. The prepared compounds were tested for antiviral activity against hepatitis B virus (HBV) which showed moderate activities.