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Syntheses of Novel Isopenam and Isocephem Antibiotics. Preparation of a retinamido derivative of a highly strained β‐lactam as potent anticancer agent
Author(s) -
Hakimelahi Gholam H.,
Shiao MinJen,
Hwu Jih Ru,
Davari Hady
Publication year - 1992
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19920750610
Subject(s) - chemistry , lactam , moiety , linker , stereochemistry , derivative (finance) , antibiotics , in vitro , biological activity , combinatorial chemistry , biochemistry , computer science , financial economics , economics , operating system
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.