Tetrahydro-β-carboline-Based Spirocyclic Lactam as Type II′ β‑Turn: Application to the Synthesis and Biological Evaluation of Somatostatine Mimetics

The synthesis of novel spirocyclic
lactams, embodying d-tryptophan (Trp) amino acid as the central
core and acting as peptidomimetics,
is presented. It relies on the strategic combination of Seebach’s
self-reproduction of chirality chemistry and Pictet–Spengler
condensation as key steps. Investigation of the conformational behavior
by molecular modeling, X-ray crystallography, and NMR and IR spectroscopies
suggests very stable and highly predictable type II′ β-turn
conformations for all compounds. Relying on this feature, we also
pursued their application to two potential mimetics of the hormone
somatostatin, a pharmaceutically relevant natural peptide, which contains
a Trp-based type II′ β-turn pharmacophore.