ABSTRACT An improved strategy for the synthesis of 2 0 -O-methyl-guanosine (6) and 2 0 -MOE-guanosine (8) is reported. The regioselectivity of the alkylation was attained using a novel silicon-based protecting group, methylene-bis (diisopropyl-silylchloride) (MDPSCl 2 , 2). The alkylation proceeded in a chemoselective manner using NaHMDS as the base and MeCl or MOE-Br as the appropriate electrophiles