- Hydrolysis of 7-Substituted Cephalosporins catalysed by β-Lactamase I and II from Bacillus cereus and by Hydroxide Ion
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Kinetic parameters are reported for the Bacillus cereus β-lactamase I- and β-lactamase II-catalysed hydrolysis of a series of thirty-seven cephalosporins substituted in the 7-position.These are compared with the second-order rate constants for the hydroxide ion-catalysed hydrolysis of these derivatives.There is no significant dependence of the rate of the base-catalysed hydrolysis upon the nature of the side-chain substituent.For β-lactamase I, kcat/Km varies over 2x105 but for β-lactamase II the variation with substituents is only 10.For alkyl substituents, kcat/Km increases with chain length and passes through a maximum, for β-lactamase I this is with the undecyl derivative and for β-lactamase II the octylcephalosporin.For β-lactamase I, but not for β-lactamase II, the t-butylcephalosporin is a very poor substrate.There is no evidence for a significant cavity in either enzyme to host aromatic residues.An ionised carboxylate residue on the side-chain significantly reduces reactivity with β-lactamase I but not β-lactamase II.It is suggested that a carboxy group on β-lactamase I acts as a general catalyst facilitating β-lactam C-N bond fission.
- Buckwell, Stephen C.,Page, Michael I.,Waley, Stephen G.,Longridge, Jethro L.
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p. 1815 - 1822
(2007/10/02)
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- Synthesis of 3-functionalised cephalosporins by photoinitiated bromination. Transformations of 2,2,2-trichloroethyl 1S, 6R, 7R)-3-bromomethyl-7-formamidoceph-3-EM-4-carboxylate, 1-oxide
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The 3-bromomethyl derivative 2c, obtained by photoinitiated bromination of the corresponding 3-Me compound 1c, has been converted into the antibiotics cephalothin 18 and cephaloridine 20. Reaction of 2c with lithium dimethyl- and diphenyl-cuprate led to the intermediates 22 and 24 respectively. Further transformation of 24 provided the 3-benzyl derivative 27, an isostere of cephaloridine.
- Cowley,Humber,Laundon,et al.
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p. 461 - 467
(2007/10/02)
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- Process for the activation of carboxylic acids
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A process for the activation of carboxylic acids which is useful for the subsequent conversion of said carboxylic acids into their corresponding amides or esters, based on reacting a 2-oxazolidinone with phosphorus pentachloride and subsequent addition of a salt of the carboxylic acid to be activated.
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