SIMPLIFIED SYNTHESIS OF 2'-O-ALKYL RIBOPYRIMIDINES

Direct 2'-hydroxyl alkylation (R= methyl, ethyl, propyl, pentyl or allyl) of 5'-dimethoxytrityl-N-(t-butylphenoxyacetyl or benzoyl)-cytidine 1 was achieved by reaction in the presence of silver I oxide and a catalytic amount of pyridine with excess alkyl halide. AT 0 degrees C alkylation of the 2'-hydroxyl was found to be highly selective; less than 10% dl (2'3')-O-alkylated or 3'-O-alkylated side products were detected in most cases. Quantitative deamination of 2'-O-alkylated cytidines to 2'-O-alkylated uridines were performed by refluxing in 4M aq. LiOH solution. This method simplifies access to various 2'-O-alkylated ribopyrimidines using readily available starting materials in one or two steps.