Divergent Chemoenzymatic Synthesis of Asymmetrical‐Core‐Fucosylated and Core‐Unmodified N ‐Glycans

A divergent chemoenzymaytic approach for the preparation of core‐fucosylated and core‐unmodified asymmetrical N ‐glycans from a common advances precursor is described. An undecasaccharide was synthesized by sequential chemical glycosylations of an orthogonally protected core fucosylated hexasaccharide that is common to all mammalian core fucosylated N ‐glycans. Antennae‐selective enzymatic extension of the undecasaccharide using a panel of glycosyl transferases afforded core fucosylated asymmetrical triantennary N ‐glycan isomers, which are potential biomarkers for breast cancer. A unique aspect of our approach is that a fucosidase (FucA1) has been identified that selectively can cleave a core‐fucoside without affecting the fucoside of a sialyl Lewis X epitope to give easy access to core‐unmodified compounds.