SYNTHESIS AND BIOLOGICAL ACTIVITY OF ALKYLIDENE-SUBSTITUTED CEPHEMS AND PENAMS
DOI:
https://doi.org/10.1007/1575Keywords:
tert-butyl esters of (6Z)-alkylidene-1, 1-dioxopenicillanic acids, tert-butyl esters of (7Z)-alkylidene-3-methyl-1, 1-dioxoceph-3-em-4-carboxylic acids, (6Z)-(N-methyl-N-methoxycarbamoylmethylidene)-1, 1-dioxopenicillanic acid, 3-methyl-(7Z)-(N-methyl-N-methoxycarbamoylmethylidene)-1, 1-dioxoceph-3-em-4-carboxylic acid, cyclic sulfones, condensation, oxidation by m-chloroperbenzoic acidAbstract
The condensation of tert-butyl esters of 3-methyl-7-oxoceph-3-em-4-carboxylic and 6-oxopenicillanic acids with a series of 2-oxoalkylidene(triphenyl)phosphoranes gave tert-butyl esters of new cephalosporin and penicillin analogs with an alkylidene substituent in the β-lactam ring. Most of these products were oxidized by meta-chloroperbenzoic acid to the corresponding sulfones. The cephemes and penams synthesized including the oxidized products displayed high cytotoxicity relative to cancer cells in vitro. Some of the alkylidene-substituted cephems as the free acids, similar to Tazobactam, inhibit the catalytic activity of Enterobacter cloacae penicillinase.
Authors: I. Potorocina, M. Vorona, I. Shestakova, I. Domracheva, E. Liepinsh, and G. Veinberg
English translation in Chemistry of Heterocyclic Compounds, 2011, 47 (6), pp 767-775
