Synthesis of 5'-O-beta-D-glucopyranosyl and 5'-O-beta-D-galactopyranosyl derivatives of ribavirin.
The synthesis of 5'-O-beta-D-glucopyranosyl and 5'-O-beta-D-galactopyranosyl derivatives (13 and 15, respectively) of the antiviral agent ribavirin are described. Direct glycosylation of 2',3'-O-isopropylideneribavirin with either tetra-O-acetyl-alpha-D-glucopyranosyl bromide (4) or tetra-O-acetyl-alpha-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-beta-D-glucopyranosyl-beta-D-ribofuranosyl)-1,2,4-triazole-3-carb oxamide (13). Similarly, reaction of 11 with 8 in the presence of AgClO4, and deprotection of the condensation product, gave 5'-O-beta-D-galactopyranosylribavirin (15). The beta-anomeric configuration of the D-glucosyl and D-galactosyl groups of 13 and 15 was assigned by 1H-n.m.r. studies.
Hanna
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Nucleic Acid Research Institute, Costa Mesa, California 92626.
Robins
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Revankar
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D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D012254:Ribavirin / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D012263:Ribonucleosides / Q000138:chemical synthesis*; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D012263:Ribonucleosides; C054020:5'-O-glucopyranosyl ribavirin; C054021:5'-O-galactopyranosyl ribavirin; D012254:Ribavirin