Selective synthesis of alpha- and beta-glycosides of N-acetyl galactosamine using rare earth metal triflates

Structures containing galactose and GalNAc residues are specifically recognized by asialoglycoprotein receptors, allowing them to selectively internalize by hepatocytes for drug-targeting delivery. However, methods for direct synthesis of GalNAc glycosides are still challenging due to the poor participating group of 2-acetamido. Here, we develop a facile strategy to synthesize various GalNAc glycosides by employing a series of rare earth metal triflates, and the results demonstrate that both alpha-glycosides and beta-glycosides of GalNAc can be obtained by conducting with Hf(OTf)(4) and Sc(OTf)(3), respectively. These applicable results indicate that any interested GalNAc-containing substrates could be prepared by this simple strategy.