3-Substituent effect and 3-methylene substituent effect on the structure-reactivity relationship of 7 beta-(acylamino)-3-cephem-4-carboxylic acid derivatives studied by carbon-13 and IR spectroscopies.
Relationships between the chemical reactivity of 3-substituted cephalosporins or 3-methylene-substituted cephalosporins and several parameters observed by 13C NMR and IR spectroscopies are described. Among 3-substituted cephalosporins, the values of delta (C-3) and delta (COO) of 13C NMR spectra are correlated with the logarithms of the rate constants for alkaline hydrolysis (log kobsd) when substituents at the 3-position are classified into two groups, i.e., OR substituents and others. Among the 3-methylene-substituted cephalosporins, the difference values of the 13C chemical shifts for C-3 and C-4, delta delta (4-3), are correlated with log kobsd. The beta-lactam vC = O value of the solution IR spectra is a good index for the prediction of a significant change of the beta-lactam reactivity resulting from modification of a 3-substituent or a 3-methylene substituent. From analysis of these observed parameters, both resonance and inductive effects of the substituent at the 3-position were found to affect the chemical reactivity of the beta-lactam ring in cephalosporin, while only the inductive effect of the substituent at the 3'-position was found to affect the beta-lactam reactivity.
D002511:Cephalosporins / Q000138:chemical synthesis* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D007202:Indicators and Reagents; D007711:Klebsiella pneumoniae / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D047090:beta-Lactams / Q000138:chemical synthesis
D002511:Cephalosporins; D007202:Indicators and Reagents; D047090:beta-Lactams