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

C-Glycosyl peptides/proteins are metabolically stable mimics of the native glycopeptides/proteins of great therapeutic potential, but their chemical synthesis is challenging. Here, the authors report a protocol for the synthesis of vinyl C-glycosyl amino acids and peptides, via a Ni-catalyzed reductive hydroglycosylation reaction of alkyne derivatives of amino acids and peptides with glycosyl bromides. 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.

Automated summary

C-Glycosyl peptides/proteins, stable mimics of native glycopeptides/proteins with therapeutic potential, have been successfully synthesized using a novel method. This synthesis approach is versatile, accommodating a wide range of coupling partners, including complex oligosaccharides and peptide substrates. The resulting vinyl C-glycosyl amino acids and peptides are amenable to further transformations for elongation of peptide and saccharide chains.