New Fluorinated Peptidomimetics through Tandem Aza-Michael Addition to α-Trifluoromethyl Acrylamide Acceptors: Synthesis and Conformational Study in Solid State and Solution

Abstract

A range of partially modified retro (PMR) psi[NHCH(2)] peptide mimetics containing a hydrolytically stable CH(2)CH(CF(3))CO unit have been synthesized. The first kind of peptidomimetics is obtained from the highly efficient aza-Michael addition of different amines to alpha-trifluoromethyl acrylamide acceptors. Subsequent deprotection of the amino group furnishes the key common intermediate for the synthesis of other families of peptidomimetics: dipeptides, tripeptides, peptidomimetics containing a urea moiety, and structures containing two units of alpha-trifluoromethyl-beta(2)-alanine. Finally, a conformational study of several of the newly synthesized peptidomimetics, performed with the aid of X-ray analysis and NMR techniques, shows a beta-turn-like conformation for the structures both in the solid state and in solution.