- Kinetics and Mechanisms of Hydrolysis and Aminolysis of Thioxocephalosporins
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The effect of replacing the β-lactam carbonyl oxygen in cephalosporins by sulfur on their reactivity has been investigated. The second-order rate constant for alkaline hydrolysis of the sulfur analogue is 2-fold less than that for the natural cephalosporin. The thioxo derivative of cephalexin, with an amino group in the C7 side chain, undergoes β-lactam ring opening with intramolecular aminolysis by a reaction similar to that for cephalexin itself. However, the rate of intramolecular aminolysis for the S-analogue is 3 orders of magnitude greater than that for cephalexin. Furthermore, unlike cephalexin, intramolecular aminolysis in the S-analogue occurs up to pH 14 with no competitive hydrolysis. The rate of intermolecular aminolysis of natural cephalosporins is dominated by a second-order dependence on amine concentration, whereas that for thioxocephalosporins shows only a first-order term in amine. The Bronsted βnuc for the aminolysis of thioxo-cephalosporin is +0.39, indicative of rate-limiting formation of the tetrahedral intermediate with an early transition state with relatively little C-N bond formation.
- Tsang, Wing Y.,Dhanda, Anupna,Schofield, Christopher J.,Page, Michael I.
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p. 339 - 344
(2007/10/03)
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- Thio-β-lactam cephalosporins
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Thio-β-lactam cephalosporins of the general formula SPC1 Wherein R is hydrogen, lower alkyl, phenyl-lower alkyl, trihaloethyl, alkali metal or alkaline earth metal; R1 is hydrogen, lower alkyl, cycloalkyl, phenyl, phenoxy, phenyl-lower alkyl or
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