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 beta-turn-like structure, the X-ray crystal structure and NMR studies indicate an open turn structure.

Peptides U 0400Synthesis of Conformationally Constrained Peptidomimetics Using Multicomponent Reactions. -A novel and rapid method to prepare biologically important products is reported. NMR and X-ray studies indicate that they adopt an open turn structure instead of the expected β-turn-like structure. -(SCHEFFELAAR, R.; KLEIN NIJENHUIS, R. A.; PARAVIDINO, M.; LUTZ, M.; SPEK, A. L.; EHLERS, A. W.; DE KANTER, F. J. J.; GROEN, M. B.; ORRU*, R. V. A.; RUIJTER, E.; J. Org. Chem. 74 (2009) 2, 660-668; Dep. Chem. Pharm. Sci., Vrije Univ., NL-1081 HV Amsterdam, Neth.; Eng.) -Jannicke 21-186