Synthesis and biological activities of the (Z) isomers of carbapenem antibiotics

Abstract
Naturally occurring carbapenem antibiotics having a double bond in the side chain, when refluxed in chloroform containing quarternary alkylammonium halides, were converted into Z isomers in high yields. The mechanism of this new equilibrium involves intramolecular proton transfer from the carboxylic acid to the C .alpha. to the S atom in the side chain as shown by 2H-labeling experiments. Some Z isomers showed stronger protective effects in mice infected by Escherichia coli 0-111 and more potent synergistic activities with cefotiam in mice infected by Proteus vulgaris GN4815 than did the naturally occurring E isomers. The decomposition rates of the Z isomers in mouse kidney homogenates were .apprx. 3-fold slower than those of the E isomers.

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