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 <i>N</i>-glycans. Due to their structural complexity, the synthesis of a comprehensive library of <i>N</i>-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 <i>N</i>-glycans containing LacdiNAc, LDNF, or 6'-SLDN epitopes. This strategy features the site-selective enzymatic preparation of two asymmetric <i>N</i>-glycan core structures, followed by diversity-oriented derivatization to provide 16 hard-to-obtain asymmetric biantennary <i>N</i>-glycans bearing LacdiNAc-related epitopes.