Syntheses of Novel Isopenam and Isocephem Antibiotics. Preparation of a retinamido derivative of a highly strained β‐lactam as potent anticancer agent

Abstract

Syntheses of the cis‐configurated isopenam 9 (Scheme 1), isocephem 14 (Scheme 2), and isocephem 19 (Scheme 3) are described. The key step in the preparation of 14 and 19 involved a Pummerer‐type rearrangement of the corresponding sulfoxides 12 and 18. These β‐lactams were found to possess biological activity against several pathogenic microorganisms in vitro. The electronic activation of the lactam moiety of 19 remarkably enhanced its biological activity. A retinoic moiety was attached to 19 via an amino linker. The resultant retinamido‐β‐lactam 21 showed significant cytostatic activity in tracheal organ cultures obtained from vitamin‐A‐deficient hamsters. Copyright © 1992 Verlag GmbH & Co. KGaA, Weinheim