Ritter-based glycoconjugation of amino acids and peptides--access to novel glycoconjugates displaying a beta-amide linkage between amino acid and sugar moiety.
Beta-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 beta-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(epsilon)-glycoconjugation of peptides on the solid phase.
Penner
Marlin
M
Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada R3T 2N2.
Schweizer
Frank
F
D000577:Amides / Q000737:chemistry*; D000596:Amino Acids / Q000138:chemical synthesis*; D002241:Carbohydrates / Q000737:chemistry*; D006001:Glycoconjugates / Q000737:chemistry*; D006020:Glycopeptides / Q000138:chemical synthesis*; D006031:Glycosylation; D015394:Molecular Structure
D000577:Amides; D000596:Amino Acids; D002241:Carbohydrates; D006001:Glycoconjugates; D006020:Glycopeptides