3264-88-8Relevant articles and documents
Investigation of a Proposed Penicillin G Acidic Degradation Scheme using High-pressure Liquid Chromatography and Optimization Techniques and Mechanistic Considerations
Kessler, David P.,Cushman, Mark,Ghebre-Sellassie, Isaac,Knevel, Adelbert M.,Hem, Stanley L.
, p. 1699 - 1704 (2007/10/02)
Optimization techniques were used to fit a recently proposed degradation scheme to recently published n.m.r. data for the time course of penicillin G and four degradation products at pH 2.5 and 37 deg C.Several conclusions arising from the n.m.r. analysis which were originally associated with the degradation scheme were not compatible with the optimized rate constants.It was necessary to change substantially the proportion of penicillin G degrading through benzylpenicillenic acid, benzylpenillic acid, and benzylpenicilloic acid in order for the degradation scheme to fit the n.m.r. data.Benzylpenillic acid replaced benzylpenicillenic acid as the major product.The rate constants best describing the n.m.r. data showed benzylpenicillenic acid proceeding almost exclusively through benzylpenamaldic acid.Such optimization implied that the scheme could be simplified to three parallel reaction pathways, the dominant reaction occurring through benzylpenillic acid.However, mechanistic considerations indicate that the direct conversion of penicillin G into benzylpenillic acid is not possible and that a likely intermediate is benzylpenicilloic acid.The degradation of benzylpenicilloic acid at pH 2.5 was consequently monitored by ionpair reversed-phase high-pressure liquid chromatography and rapid formation of benzylpenillic acid was detected.This observation is inconsistent with the recently proposed degradation scheme, even though the scheme can be made to fit the n.m.r. kinetic data.
The Chemical Reactivity of Penicillins and Other β-Lactam Antibiotics
Proctor, Philip,Gensmantel, Nigel P.,Page, Michael I.
, p. 1185 - 1192 (2007/10/02)
The rates of the acid catalysed hydrolysis of penicillins and cephalosporins are linear in Ho and, unlike other amides, show no rate maximum with increasing acidity.Electron-withdrawing substituents at C-6 in penicillins decrease the rate of hydrolysis with a ρI of ca. 4 and they decrease the rate when attached to the amine leaving group.The acylamido-group at C-6 in penicillins, but not at C-7 in cephalosporins, exhibits neighbouring group participation with a rate enhancement of ca. 103.The absence of penicillenic acid formation from benzylpenicillin in acidic solution is not due to the ionisation of the carboxy-group.These observations are rationalised by a scheme involving N-protonation and formation of an acylium ion intermediate.The alkaline hydrolysis of penicillins proceeds 102 faster than a β-lactam after correction for substituent effects.There is no evidence for substantial inhibition of amide resonance in the bicyclic β-lactam antibiotics, little evidence to indicate extra strain in these systems and no evidence that expulsion of the leaving group at C-3 in cephalosporins occurs in the transition state.
