Synthesis and biological activities of the Z isomers of carbapenem antibiotics

Article abstract of DOI:10.1021/jm00356a029

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 equilibration involves intramolecular proton transfer from the carboxylic acid to the carbon α to the sulfur atom in the side chain as shown by deuterium-labeling experiments. Some Z isomers showed stronger protective effects in mice infected by Escherichia coli O-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 about 3-fold slower than those of the E isomers.