Synthesis and Anti-Hepatitis B Virus Activity of Glucosylated 2- O -Ethyluracils

Abstract

2-O-Ethyluracils were silylated with HMDS and condensed in the presence of TMS-triflate with β-D-glucose pentaacetate to give the corresponding β-nucleosides. Alternatively, these could be synthesized by nucleoside coupling of 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide with the sodium salts of 2-O-ethyluracils, which were deprotected with saturated ammonia in methanol. 6′-O-Tosylate nucleoside derivatives were prepared by treating of the latter with tosyl chloride in anhydrous pyridine. The compounds thus obtained were treated with sodium azide in anhydrous DMF to afford the corresponding 6′-azido nucleoside derivatives, which can also be prepared by treatment with sodium azide in the presence of carbon tetrabromide and triphenylphosphine in anhydrous DMF. Nucleophilic displacement of the 6′-tosyloxy group by morpholine gave 6′-deoxy-6′-morpholino nucleosides. The reduction of the azido group of the 6′-azido nucleosides using triphenylphosphine in pyridine afforded the 6′-amino analogues. Glucosylated 2-O-ethyluracils showed moderate activity against HBV.