N-Difluoromethyl-triazole as a constrained scaffold in peptidomimetics

The N-difluoromethyl triazolo-β-aza-ε-amino acid present in the core of peptides led to constrained conformations due to CH-F and NH-F interactions. Pseudotetrapeptides were obtained in excellent yields directly by click chemistry between azidodifluoroacetamides and alkynes, both linked to an amino acid. This work demonstrates that the N-difluoromethyltriazole scaffold can induce extended structures to β-strand mimics.