Chemoenzymatic Synthesis of Core‐Fucosylated Asymmetrical <i>N</i> ‐Glycans with Different‐Length Oligo‐ <i>N</i> ‐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 is 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 were 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.