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.
Tetrahydro-β-carboline-based spirocyclic lactam as type II' β-turn : application to the synthesis and biological evaluation of somatostatine mimetics / G. Lesma, R. Cecchi, A. Cagnotto, M. Gobbi, F. Meneghetti, M. Musolino, A. Sacchetti, A. Silvani. - In: JOURNAL OF ORGANIC CHEMISTRY. - ISSN 0022-3263. - 78:6(2013), pp. 2600-2610. [10.1021/jo302737j]
Tetrahydro-β-carboline-based spirocyclic lactam as type II' β-turn : application to the synthesis and biological evaluation of somatostatine mimetics
G. LesmaPrimo
;F. Meneghetti;M. Musolino
;A. SilvaniUltimo
2013
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.File | Dimensione | Formato | |
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