Synthesis and 3'-substituent effects of some 7.alpha.-methoxy-1-oxacephems on antibacterial activity and alkaline hydrolysis rates

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Abstract
Relationships between intrinsic antibacterial activity and .beta.-lactam chemical reactivity of 7.beta.-(phenylactamido)-7.alpha.-methoxy-1-oxacephems with various 3''-substituents (1-9) were studied in order to clarify the effect of the 3''-substituent on the antibacterial activity. The chemical reactivity of the .beta.-lactamring estimated by pseudo-first-order rate constants log kobsdNMR of alkaline hydrolyisis at pD 10.4 and 35.0.degree.C correlates well linearly with 13C NMR chemical shift differences (.DELTA..delta.(4-3)), infrared stretching frequencies of the .beta.-lactam carbonyl (vC .sigma. O), and .sigma.i values. Values of log (1/CN), averaged for the MIC values for Escherichia coli, E. coli NIH JC-2, E. coli EC-14, and Klebsiella pneumoniae SRC-1, were taken as an estimation of the intrinsic antibacterial. The log (1/CN) values of the compounds without good leaving groups (1, 2, 4,5, and 8) correlated fairly well with logobsdNMR values of the compounds with good leaving groups (6, 7, and 9) may be attributable to the different course of decomposition of these compounds.

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