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

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.