Synthesis of 5′- O-β- d-glucopyranosyl and 5′- O-β- d-galactopyranosyl derivatives of ribavirin

Abstract

The synthesis of 5′- O-β- d-glucopyranosyl and 5′- O-β- d-galactopyranosyl derivatives ( 13 and 15, respectively) of the antiviral agent ribavirin are descrobed. Direct glycosylation of 2′,3′- O-isopropylideneribavirin with either tetra- O-acetyl-α- d-glucopyranosyl bromide ( 4) or tetra- O-acetyl-α- d-galactopyranosyl bromide ( 8) under Koenigs-Knorr conditions ( i.e., silver carbonate, silver perchlorate, and Drierite in dichloromethane) followed by O-deacetylation of the reaction product gave the corresponding ortho esters. However, treatment of 2′,3′-di- O-acetyl-5′- O-tritylribavirin ( 11) with 4 under the Bredereck modification of the Koenigs-Knorr reaction ( i.e., silver perchlorate and Drierite in nitromethane) and subsequent deacetylation furnished the desired 1(5- O-β- d-glucopyranosyl-β- d-ribofuranosyl)-1,2,4-triazole-3-carboxamide ( 13). Similarly, reaction of 11 with 8 in the presence of AgClO 4, and deprotection of the condensation product, gave 5′- O-β- d-galactopyranosylribavirin ( 15). The β-anomeric configuration of the d-glucosyl and d-galactosyl groups of 13 and 15 was assigned by 1H-n.m.r. studies. ▪