Synthesis of conformationally constrained peptidomimetics using multicomponent reactions

Abstract

A novel modular synthetic approach toward constrained peptidomimetics is reported. The approach involves a highly efficient three-step sequence including two multicomponent reactions, thus allowing unprecedented diversification of both the peptide moieties and the turn-inducing scaffold. The turn-inducing properties of the dihydropyridone scaffold were evaluated by molecular modeling, X-ray crystallography, and NMR studies of a resulting peptidomimetic. Although modeling studies point toward a type IV β-turn-like structure, the X-ray crystal structure and NMR studies indicate an open turn structure.