Recent Advances in Neu5Ac α 2‐6GlcNAc: An Atypical Sialoside Motif with Emerging Biological Significance

The α 2‐6sialylation of N ‐acetylglucosamine (Neu5Ac α 2‐6GlcNAc) is an atypical sialylation linkage that has attracted increasing attention due to its unusual occurrence and biological importance. Although relatively rare, it has been identified in human milk oligosaccharides (HMOs), glycoproteins, and glycosphingolipids. Early chemical methodologies and recent chemoenzymatic advances have enabled the preparation of bioactive molecules containing the Neu5Ac α 2‐6GlcNAc motif, thereby facilitating studies of their roles in immune recognition, cancer progression, and neonatal health. This Concept highlights recent progress in synthetic strategies to access structures containing this atypical motif and discusses its emerging significance as both a subject of fundamental glycobiology and a potential target for biomedical applications.