title: Tetrahydro-β-carboline-based spirocyclic lactam as type II' β-turn: application to the synthesis and biological evaluation of somatostatine mimetics.
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.
authors: Dipartimento di Chimica, Università degli Studi di Milano, via C. Golgi 19, 20133 Milano, Italy.
authors: Giordano
authors: G
authors: Lesma
authors: Roberto
authors: R
authors: Cecchi
authors: Alfredo
authors: A
authors: Cagnotto
authors: Marco
authors: M
authors: Gobbi
authors: Fiorella
authors: F
authors: Meneghetti
authors: Manuele
authors: M
authors: Musolino
authors: Alessandro
authors: A
authors: Sacchetti
authors: Alessandra
authors: A
authors: Silvani
mesh_terms: D002243:Carbolines / Q000737:chemistry*; D018360:Crystallography, X-Ray; D007769:Lactams / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D057786:Peptidomimetics / Q000138:chemical synthesis* / Q000737:chemistry; D013004:Somatostatin / Q000138:chemical synthesis* / Q000737:chemistry; D013141:Spiro Compounds / Q000737:chemistry*; D014364:Tryptophan / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D002243:Carbolines; D007769:Lactams; D010455:Peptides; D057786:Peptidomimetics; D013141:Spiro Compounds; D013004:Somatostatin; D014364:Tryptophan