Stereoselective Synthesis of 1,2‐cis O‐linked Glycosyl Amino Acids via Additive‐Modulation for Glycopeptide Synthesis

A highly stereoselective strategy to facilitate the synthesis of 1,2‐cis‐O‐linked glycosyl amino acids was established via a additive‐modulated trichloroacetimidate glycosylation approach. This mild and practical protocol demonstrates broad applicability with diverse glycosyl donors, including D‐gluco‐, D‐galacto‐, 2‐deoxy‐2‐azido‐D‐gluco‐, 2‐deoxy‐2‐azido‐D‐galacto‐, D‐xylo‐, L‐fuco‐pyranosyl and L‐arabinofuranosyl trichloroacetimidates, and orthogonally protected amino acids such as Ser, Thr, Tyr, and 4‐hydroxyproline (Hyp) as acceptors. These 1,2‐cis linked glycosyl amino acids serve as valuable building blocks for glycopeptide synthesis via solid‐phase peptide synthesis (SPPS), offering significant potential for advancing glycoprotein research.