Tetrahydroisoquinoline-based spirocyclic lactam as a type II' beta-turn inducing peptide mimetic.
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.
Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano, via G. Venezian 21, 20133 Milano, Italy.
Giordano
G
Lesma
Nicola
N
Landoni
Tullio
T
Pilati
Alessandro
A
Sacchetti
Alessandra
A
Silvani
D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D007546:Isoquinolines / Q000737:chemistry*; D007769:Lactams / Q000737:chemistry*; D008958:Models, Molecular; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
D007546:Isoquinolines; D007769:Lactams; D010455:Peptides