A simple procedure for the monomethylation of protected and unprotected ribonucleosides in the 2'-O- and 3'-O-position using diazomethane and the catalyst stannous chloride

Intensive studies on the diazomethane methylation of the common ribonucleosides uridine, cytidine, adenosine, and guanosine and its derivatives were performed to obtain preferentially the 2'-O-methyl isomers. Methylation of 5'-O-(monomethoxytrityl)-N-2-[2-(4-nitrophenyl)ethoxycarbonyl]-O-6-[2-(4-nitrophenyl)ethyl]guanosine (1) with diazomethane resulted in an almost quantitative yield of the 2'- and 3'-O-methyl isomers which could be separated by simple silica-gel flash chromatography (Scheme 1). Adenosine, cytidine, and uridine were methylated with diazomethane with and without protection of the 5'-O-position by a mono- or dimethoxytrityl group and the aglycone moiety of adenosine and cytidine by the 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) group (Schemes 2-4). Attempts to increase the formation of the 2'-O-methyl isomer as much as possible were based upon various solvents, temperatures, catalysts, and concentration of the catalysts during the methylation reaction.