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

A range of partially modified retro (PMR) ψ[NHCH2] peptide mimetics containing a hydrolytically stable CH2CH(CF3)CO unit have been synthesized. The first kind of peptidomimetics is obtained from the highly efficient aza-Michael addition of different amines to α-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 α-trifluoromethyl-β2-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 β-turn-like conformation for the structures both in the solid state and in solution.