Synthesis and biological activities of the Z isomers of carbapenem antibiotics.
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 alpha 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.
D000818:Animals; D001681:Biological Assay; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy; D007202:Indicators and Reagents; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D011512:Proteus Infections / Q000188:drug therapy; D011514:Proteus vulgaris / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013329:Structure-Activity Relationship; D013845:Thienamycins / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use
D007202:Indicators and Reagents; D013845:Thienamycins