An Alkyne Rod to Constrain a Peptide Backbone in an Extended Conformation

Abstract

An N,N′‐bound rod‐shaped diyne bridge was introduced into a peptide to constrain the peptide backbone in an extended conformation. Linear precursors were achieved via solid‐phase synthesis using simple commercially available building blocks. Subsequently, 13‐ to 15‐membered peptide macrocycles were obtained in excellent crude purity via in solution copper‐catalyzed cyclization. Density functional theory calculations of the lowest energy conformers suggested that the strain inside the macrocycle caused only slight deformation of the binding angles of the butadiyne moiety.