Synthesis and determination of antiviral activity of the 2'(3')-O-methyl derivatives of ribavirin (1-.beta.-D-ribofuranosyl-1,2,4-triazole-3-carboxamide)
Diazomethane treatment of ribavirin (1-.beta.-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) in the presence of SnCl2 as catalyst led to quantitative formation of the 2''-O-methyl and 3''-O-methyl derivatives of the parent compound. The products were successfully fractionated on a basic ion-exchange column and isolated in crystalline form. Identification was based on the elution sequence from the column and on 1H NMR spectroscopy. Both derivatives were inactive, relative to the parent compound, against several virus types [vesicular stomatitis, herpes simplex, vaccinia, polio and Coxsackie] in cell culture. Unlike ribavirin itself, the 2''(3'')-O-methyl derivatives did not suppress cellular DNA synthesis. NMR data showed that the loss of biologic activity on 2''(3'')-O-methylation was not due to a change of conformation of the nucleoside sugar moiety.