Solution-Phase Synthesis with Solid-State Workup of an O-Glycopeptide with a Cluster of Cancer-Related T Antigens

An N-terminal glycopeptide of asialoglycophorin AM with three O-linked T antigens was prepared by “solution-phase synthesis with solid-state workup” using unprotected glycosyl amino acids as building blocks. For the glycopeptide assembly, all reactions were conducted in homogeneous NMP solutions, while the product of each reaction was readily isolated as solid precipitates upon addition of diethyl ether. In the preparation of building blocks, a robust approach was established to selectively α-glycosylate Ser and Thr derivatives.