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

被引:19
作者
Colombo, L
Di Giacomo, M
Brusotti, G
Sardone, N
Angiolini, M
Belvisi, L
Maffioli, S
Manzoni, L
Scolastico, C
机构
[1] Univ Pavia, Pharmaceut Chem Dept, I-27100 Pavia, Italy
[2] Univ Pavia, CGS, I-27100 Pavia, Italy
[3] Univ Milan, CNR, Ctr Study Organ & Nat Cpds, I-20133 Milan, Italy
关键词
D O I
10.1016/S0040-4020(98)00207-5
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
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. (C) 1998 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:5325 / 5336
页数:12
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