Facile access to C-glycosyl amino acids and peptides via Ni-catalyzed reductive hydroglycosylation of alkynes

Abstract C -Glycosyl peptides/proteins are metabolically stable mimics of the native glycopeptides/proteins bearing O / N -glycosidic linkages, and are thus of great therapeutical potential. Herein, we disclose a protocol for the syntheses of vinyl C -glycosyl amino acids and peptides, employing a nickel-catalyzed reductive hydroglycosylation reaction of alkyne derivatives of amino acids and peptides with common glycosyl bromides. It accommodates a wide scope of the coupling partners, including complex oligosaccharide and peptide substrates. The resultant vinyl C -glycosyl amino acids and peptides, which bear common O / N -protecting groups, are amenable to further transformations, including elongation of the peptide and saccharide chains.