Diversity-Oriented Enzymatic Modular Synthesis of <i>N</i> -Glycans Bearing LacdiNAc-Related Epitopes

The disaccharide unit GalNAcβ1,4GlcNAc (LacdiNAc or LDN) and its α1,3-fucosylated derivative LDNF and α2,6-sialylated derivative 6′-SLDN are common epitopes of various N-glycans. Due to their structural complexity, the synthesis of a comprehensive library of N-glycans bearing LacdiNAc-related epitopes remains a significant challenge. Herein, we present a highly efficient enzymatic modular assembly strategy for the collective synthesis of 22 biantennary N-glycans containing LacdiNAc, LDNF, or 6′-SLDN epitopes. This strategy features the site-selective enzymatic preparation of two asymmetric N-glycan core structures, followed by diversity-oriented derivatization to provide 16 hard-to-obtain asymmetric biantennary N-glycans bearing LacdiNAc-related epitopes.