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 revea led to have a potential as reverse-turn mimetics. The convergence of t he synthetic sequence was achieved by attachment of a properly substit uted malonate unit to the (2S)-cis-5-(2-hydroxyethyl)proline tert-buty l ester, Stereoselective intramolecular alkylation of the malonate aff orded the 6-membered lactam fused to the 2-carbalkoxy pyrrolidine nucl eus. X-ray diffraction analysis of a more advanced synthetic derivativ e allowed the unequivocal assignment of the configuration at the newly created quaternary stereocenter as R. (C) 1998 Elsevier Science Ltd. All rights reserved.