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°C alkylation of the 2′-hydroxyl was found to be highly selective; less than 10% di (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.