Design and synthesis of conformationally constrained Tn antigen mimics

Conformationally constrained Tn antigen mimics have been designed with consideration of the role water plays in organizing the GalNAc with the peptide. The synthesis of the mimic is reported and employs a cross-metathesis to construct the carbon skeleton and a Tsuji-Trost cyclization to form the C-alkenyl-galactoside. An oxime cyclization onto the pendant alkene and reduction to the isoxazolidine provides a fused ring system constraining the orientation of the GalNAc residue with the underlying amino acid.