Ortho-(1-phenylvinyl)benzyl glycosides: Ether-type glycosyl donors for the efficient synthesis of both O-glycosides and nucleosides

Abstract

Both O-glycosides and nucleosides are essential biomolecules with important roles in a variety of biological processes. Chemical synthesis of both O-glycosides and nucleosides is a scalable and reliable method to develop new therapeutic agents and decipher their functions. However, the efficient synthesis of both O-glycosides and nucleosides remains one of long-standing challenges in chemical synthesis. In particular, ether-type glycosyl donors are rarely developed to achieve the efficient synthesis of both O-glycosides and nucleosides due to the stronger conditions required for breaking of the glycosidic C–O bond. Here we report that ortho-(1-phenylvinyl)benzyl glycosides are new ether-type donors for efficient synthesis of both O-glycosides and nucleosides under mild reaction conditions. This glycosylation method enables glycosylation with both alcoholic acceptors and nucleobases with a variety of reactive functionalities. Furthermore, the latent-active synthesis of glycans and the efficient synthesis of nucleosides antibiotics have also been successfully demonstrated in the current glycosylation protocol, thereby representing an important step toward streamlining the chemical synthesis of both O-glycosides and nucleosides.