title: Comparative reactivity of 1-carba-1-dethiacephalosporins with cephalosporins.
abstract: Nine matched pairs of cephalosporins and their 1-carba-1-dethiacephalosporin analogues have been compared with regard to microbiological activity, beta-lactam carbonyl infrared absorption, and aqueous stability. In general the microbiological activity of the pairs of compounds were very similar across a broad range of bacteria. The infrared absorption bands for the beta-lactam carbonyls of the pairs indicated a general trend for the 1-carba-1-dethiacephalosporins to absorb at lower frequencies than the corresponding cephalosporins. All of the 1-carba-1-dethiacephalosporins did however present a striking stability enhancement over their cephalosporin counterparts at pH = 10 or 11 in water. This marked contrast of MIC similarity with the observed differences in chemical reactivity clearly demonstrates hydroxide ion catalyzed hydrolysis is not a good model for transpeptidase activity unless the compounds comprise a limited domain of structural type.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
authors.forename: L C
authors.initials: LC
authors.lastname: Blaszczak
authors.forename: R F
authors.initials: RF
authors.lastname: Brown
authors.forename: G K
authors.initials: GK
authors.lastname: Cook
authors.forename: W J
authors.initials: WJ
authors.lastname: Hornback
authors.forename: R C
authors.initials: RC
authors.lastname: Hoying
authors.forename: J M
authors.initials: JM
authors.lastname: Indelicato
authors.forename: C L
authors.initials: CL
authors.lastname: Jordan
authors.forename: A S
authors.initials: AS
authors.lastname: Katner
authors.forename: M D
authors.initials: MD
authors.lastname: Kinnick
authors.forename: J H
authors.initials: JH
authors.lastname: McDonald
mesh_terms: D002511:Cephalosporins / Q000032:analysis / Q000138:chemical synthesis / Q000494:pharmacology*; D006868:Hydrolysis; D008826:Microbial Sensitivity Tests; D013055:Spectrophotometry, Infrared
chemical_list: D002511:Cephalosporins; C026739:carbacephems