Direct and efficient synthesis of nucleosides through the ortho-(tert-butylethynyl)phenyl thioglycosides (BEPTs) protocol.

Abstract

Nucleosides are highly biologically relevant compounds, and are widely clinically used as drugs for the treatment of virus/bacteria infections and cancers. However, efficient chemical synthesis of nucleoside is highly difficult due to the low reactivity of nucleobases acceptors, challenging the existing synthetic protocols. Here we show an alternative synthetic protocol with judiciously designed o-(tert-butylethynyl)phenyl thioglycosides (BEPTs) as donors. The protocol is featured by stable glycosylation donors and high efficiency, direct glycosylation without the need for preactivation/silylation of nucleobases, broad substrate scope, capacity in furnishing 2-deoxy-nucleosides, cost efficiency, scalability, and significantly improved reaction speed, and exhibits favorable and profound solvent effects for hexafluoroisopropanol (HFIP). To check the practicality of the protocol, efficient preparation of angustmycin A and dJ is accomplished. The reaction mechanisms are systematically investigated, providing deep insights to the BEPT protocol.