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Tetrahydroisoquinoline-based spirocyclic lactam as a type II' beta-turn inducing peptide mimetic
Giordano Lesma1, Nicola Landoni, Tullio Pilati
1Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano, via G. Venezian 21, 20133 Milano, Italy.
Abstract:
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' beta-turn conformations.
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