Chemoenzymatic Synthesis of Core‐Fucosylated Asymmetrical N‐Glycans with Different‐Length Oligo‐N‐Acetyllactosamine Motifs and Their Sialylated Extensions

An efficient chemoenzymatic approach for the diversity‐oriented synthesis of core‐fucosylated asymmetrical N‐glycans bearing different lengths of oligo‐N‐acetyllactosamine (LacNAc) and their sialylated extensions was described. Two oligosaccharide precursors were chemically synthesized by length‐controlled introduction of oligo‐LacNAc motifs through stereoselectively iterative glycosylation of a common hexasaccharide intermediate. Both oligosaccharide precursors can be well recognized by α1,6‐fucosyltransferase FUT8 to generate core‐fucosylated N‐glycans, which was subjected to divergent enzymatic extension using a galactosyltransferase module and two sialyltransferase modules to provide a wide array of core‐fucosylated asymmetrical biantennary N‐glycans having different‐length oligo‐LacNAc motifs capped by various sialic acid‐linkages.