Comparative reactivity of 1-carba-1-dethiacephalosporins with cephalosporins.
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.
Blaszczak
L C
LC
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
Brown
R F
RF
Cook
G K
GK
Hornback
W J
WJ
Hoying
R C
RC
Indelicato
J M
JM
Jordan
C L
CL
Katner
A S
AS
Kinnick
M D
MD
McDonald
J H
JH
D002511:Cephalosporins / Q000032:analysis / Q000138:chemical synthesis / Q000494:pharmacology*; D006868:Hydrolysis; D008826:Microbial Sensitivity Tests; D013055:Spectrophotometry, Infrared
D002511:Cephalosporins; C026739:carbacephems