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 (2S)-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.
Stereoselective synthesis of 6,5-bicyclic reverse-turn peptidomimetics / L. Colombo, M. Di Giacomo, G. Brusotti, N. Sardone, M. Angiolini, L. Belvisi, S. Maffioli, L. Manzoni, C. Scolastico. - In: TETRAHEDRON. - ISSN 0040-4020. - 54:20(1998), pp. 5325-5336.
Stereoselective synthesis of 6,5-bicyclic reverse-turn peptidomimetics
L. Belvisi;S. Maffioli;L. Manzoni;C. Scolastico
1998
Abstract
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 (2S)-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.Pubblicazioni consigliate
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