Synthesis of a galacto-configured C-ketoside-based γ-sugar-amino acid and its use in peptide coupling reactions

γ-Sugar-amino acid analogues in the form of C-ketosides can be prepared in 5–6 steps starting from d-galactono-1,5-lactone. The key step in the synthesis is the trimethylsilyl trifluoromethanesulfonate (TMSOTf) promoted C-glycosylation of 2-deoxy-3-ulopyranosonates with trimethylsilyl cyanide. Hydrogenation of the resulting β-cyano esters provides C-ketoside-based γ-sugar-amino acids that serve as building blocks for the synthesis of unnatural neoglycopeptides.