title: Synthesis and biological evaluation of optically active 3-H-1-carbacephem compounds.
abstract: 3-H-1-Carbacephem nuclei with or without a 2 alpha- or 2 beta-methyl group were prepared via 2 + 2 cycloaddition followed by intramolecular Horner-Emmons cyclization. Optically active 3-H-1-carbacephem compounds were efficiently prepared by employing a penicillin acylase-producing microorganism in two ways. That is, the 7-phenylacetamide of a racemic carbacephem nucleus was hydrolyzed enantioselectively with the enzyme to afford the optically pure nucleus, which was then acylated to give antimicrobial compounds. Alternatively, a racemic carbacephem nucleus was directly and enantioselectively phenylglycylated with the enzyme. 3-H-1-Carbacephem nuclei appeared to be better substrates for penicillin acylase than penam or cephem nuclei of natural origin. 3-H-1-Carbacephem compounds showed potent antimicrobial activity; compound 32a exhibited activity comparable to that of ceftizoxime, a cephem analog with the same acyl group. It is of interest that the 3-H-1-carbacephem compound turned out to have more potent antimicrobial activity than its 3-substituted methyl analog.
authors.forename: T
authors.initials: T
authors.lastname: Ogasa
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: Y
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Hirata
mesh_terms: D001419:Bacteria / Q000187:drug effects; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D008826:Microbial Sensitivity Tests
chemical_list: D002511:Cephalosporins; C026739:carbacephems