Toward N-Linked Glycoproteins: Three-Step Synthesis of Glycan-Asparagine Conjugates from Unprotected Sugars

We have developed a three-step method to synthesize glycan-asparagine conjugates, a core structural motif of N-linked glycoproteins, directly from unprotected saccharides. This transformation involves preparing carbamoyl radical precursors via anomeric amination and condensation without protection, followed by visible-light-mediated carbamoyl radical addition to dehydroalanine derivatives. Characterized by its broad substrate scope, including sialylated glycans and bioactive peptides, and compatibility with buffered aqueous media, this methodology potentially provides a practical platform for the late-stage glycosylation of proteins.