Tetrahydro-β-carboline-based spirocyclic lactam as type II' β-turn: application to the synthesis and biological evaluation of somatostatine mimetics

J Org Chem. 2013 Mar 15;78(6):2600-10. doi: 10.1021/jo302737j. Epub 2013 Feb 21.

Abstract

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.

MeSH terms

  • Carbolines / chemistry*
  • Crystallography, X-Ray
  • Lactams / chemistry*
  • Magnetic Resonance Spectroscopy
  • Molecular Conformation
  • Peptides / chemical synthesis*
  • Peptides / chemistry*
  • Peptidomimetics / chemical synthesis*
  • Peptidomimetics / chemistry
  • Somatostatin / chemical synthesis*
  • Somatostatin / chemistry
  • Spiro Compounds / chemistry*
  • Tryptophan / chemical synthesis*
  • Tryptophan / chemistry

Substances

  • Carbolines
  • Lactams
  • Peptides
  • Peptidomimetics
  • Spiro Compounds
  • Somatostatin
  • Tryptophan