Glycosylation of Nucleosides.

Abstract

Nucleoside O-glycosylation represents an archetypal problem in chemical selectivity, inasmuch as the nucleobase (an undesired site of reaction) is usually more nucleophilic than the hydroxyl (the desired site of reaction). Optimized reaction conditions have been developed for the efficient O-glycosylation of nucleoside hydroxyls. Both thioglycoside and Schmidt imidate donors (1.5 equiv) have been employed successfully. Interference by the nucleobase is minimized by the use of indium(III) triflate as the donor activating reagent; the In(OTf)3 serves to promote apparent transfer of the donor glycosyl moiety from nucleobase to hydroxyl. Glycosylation of uridine triacetate gives products resulting from O- and N-glycosylation of the pyrimidine ring.