Selective synthesis of α- and β-glycosides of N-acetyl galactosamine using rare earth metal triflates

Jiajia Wang; Wei Zhang; Wei Cao; Kang Liu; Shihao Su; Jing Ma; Xia Li

doi:10.3389/fchem.2022.1029911

Selective synthesis of α- and β-glycosides of N-acetyl galactosamine using rare earth metal triflates

Front Chem. 2022 Oct 26:10:1029911. doi: 10.3389/fchem.2022.1029911. eCollection 2022.

Authors

Jiajia Wang¹, Wei Zhang², Wei Cao¹, Kang Liu¹, Shihao Su², Jing Ma², Xia Li¹

Affiliations

¹ Joint National Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, Henan University, Kaifeng, Henan, China.
² School of Pharmacy, Academy for Advanced Interdisciplinary Studies, Institute of Chemical Biology, Henan University, Kaifeng, Henan, China.

Abstract

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 α-glycosides and β-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.

Keywords: GalNAc; asialoglycoprotein receptor (ASGPR); glycosylation; hydrogen sulfide; selective.