Ritter-based glycoconjugation of amino acids and peptides—access to novel glycoconjugates displaying a β-amide linkage between amino acid and sugar moiety

β-Peptidic-d-gluco-, d-galacto-, and l-fuco-configured glycosyl amino acids can be prepared from the corresponding 2-deoxy-oct-3-ulopyranosonic acids via a one-pot intramolecular Ritter reaction. Initially, a ketopyranoside-based acid condenses under Lewis acid promoted conditions with nitriles (PhCN, MeCN) and a partially protected diamino ester (Boc-DAB-O-t-Bu, Boc-Orn-O-t-Bu) to form a β-peptidic glycosyl amino t-butylesters. The glycosyl amino t-butylesters can be converted into Fmoc-protected glycosyl amino acids that are suitably protected for solid-phase glycopeptide synthesis. Furthermore, replacement of the protected diamino ester by immobilized peptide amines permits post-synthetic N-terminal- and N(ε)-glycoconjugation of peptides on the solid phase.

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