Tetrahydroisoquinoline-Based Spirocyclic Lactam as a Type II’ β-Turn Inducing Peptide Mimetic

(Chemical Equation Presented) We present here spirocyclic lactam derivatives, embodying D-Phe and L-Ala amino acids as the central core and acting as tetrapeptide and hexapeptide mimetics. An efficient route for their synthesis is demonstrated by using the strategic combination of Seebach's self-reproduction of chirality chemistry and the Pictet-Spengler condensation as key steps. The conformational behavior of peptide mimetics was investigated by molecular modeling, X-ray crystallography, NMR (solvent and temperature dependence), IR spectroscopy, and circular dichroism. All data suggest very stable and highly predictable type II′ β-turn conformations.