SYNTHESIS AND CYTOTOXIC PROPERTIES OF DERIVATIVES OF THE <i>tert</i>-BUTYL ESTER OF 7-ALKYLIDENE-3-METHYL-3-CEPHEME-4-CARBOXYLIC ACID

Abstract

Sulfones of the tert-butyl esters of 7-arylmethylene- and 7-(2-furyl)methylene-3-methyl-3-cepheme-4-carboxylic acid were obtained by the condensation of the tert-butyl ester of 3-methyl-7-oxo-3-cepheme-4-carboxylic acid with arylmethylene- and 2-furylidenetriphenylphosphoranes and subsequent oxidation of the intermediate products by meta-chloroperbenzoic acid. The combination of the tert-butyl esters of 7E-bromomethylene- and 7,7-dibromomethylene-3-methyl-1,1-dioxo-3-cepheme-4-carboxylic acids with trimethylsilylacetylene  under conditions of the Sonogashira reaction gave the tert-butyl esters of 3-methyl-1,1-dioxo-7E-(3-trimethylsilyl-2-propynylidene)-3-cepheme-4-carboxylic acid and 3-methyl-1,1-dioxo-7-[1,5-bis(trimethylsilyl)-1,4-pentadiyn-3-ylidene]-3-cepheme-4-carboxylic acid. The Vilsmeier reagent was used to incorporate the dimethylaminomethylene group at C-2 of the 7Z- and 7E-isomers of the tert-butyl ester of 7-(4-chlorophenyl)methylene-3-methyl-1,1-dioxo-3-cepheme-4-carboxylic acid. The cytotoxic properties of the  derivatives of the tert-butyl ester of 7-alkylidene-3-methyl-3-cepheme-4-carboxylic acid in regard to cancer and normal cells in vitro depends on the structure and 7Z- or 7E-isomerism of the substituent in the 7-alkylidene group as well as the presence of a dimethylaminomethylene group at C-2 of the 3-cepheme system.

How to Cite
Vorona, M.; Potorocina, I.; Veinberg, G.; Shestakova, I.; Kanepe, I.; Lukevics, E.  Chem. Heterocycl. Compd. 2008, 44, 739. [Khim. Geterotsikl. Soedin. 2008, 918.]

For this article in the English edition see DOI 10.1007/s10593-008-0099-0