Novel synthesis of 2′-O-methylguanosine

An efficient and chemoselective synthesis of 2′-O-methylguanosine (6) has been accomplished in high yield without protection of the guanine base. The salient feature of the synthesis of 6 lies in the application of methylene-bis-(diisopropylsilyl chloride), (MDPSCl2, 2) as a new 3′,5′-O-protecting group for nucleosides. Use of CH3Cl as a weak electrophile and NaHMDS as a mild base was crucial to the success of the 2′-O-methylation of 3′,5′-O-protected guanosine.