Stereoselective synthesis of 6,5-bicyclic reverse-turn peptidomimetics

A flexible stereoselective synthetic scheme was developed to prepare 6,5-fused bicyclic lactams, that molecular mechanics calculations revealed to have a potential as reverse-turn mimetics. The convergence of the synthetic sequence was achieved by attachment of a properly substituted malonate unit t...

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Bibliographic Details
Published in:Tetrahedron 1998-05, Vol.54 (20), p.5325-5336
Main Authors: Colombo, Lino, Di Giacomo, Marcello, Brusotti, Gloria, Sardone, Nicola, Angiolini, Mauro, Belvisi, Laura, Maffioli, Sonia, Manzoni, Leonardo, Scolastico, Carlo
Format: Article
Language:English
Subjects:
Bicyclic aliphatic compounds
Conformation
Lactams
Peptide mimetics
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Summary:A flexible stereoselective synthetic scheme was developed to prepare 6,5-fused bicyclic lactams, that molecular mechanics calculations revealed to have a potential as reverse-turn mimetics. The convergence of the synthetic sequence was achieved by attachment of a properly substituted malonate unit to the (2 S)- cis-5-(2-hydroxyethyl)proline tert-butyl ester. Stereoselective intramolecular alkylation of the malonate afforded the 6-membered lactam fused to the 2-carbalkoxy pyrrolidine nucleus. X-ray diffraction analysis of a more advanced synthetic derivative allowed the unequivocal assignment of the configuration at the newly created quaternary stereocenter as R. Graphic
ISSN:0040-4020
1464-5416
DOI:10.1016/S0040-4020(98)00207-5