- Thiazolidine Ring Opening in Penicillin Derivatives. Part 2. Enamine Formation
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The alkaline hydrolysis of (3S,5R,6R)-methyl benzylpenicilloate, and the corresponding carboxamide and N-ethylamide, is accompanied by an absorbance increase at 285 nm.This is attributed to a competing elimination reaction across C6-C5 to open the thiazolidine ring and reversibly generate an enamine intermediate.Kinetic analysis and hydrolysis in D2O do not indicate a significant buildup of this intermediate during hydrolysis of the methyl ester.However, over the pH range 4-11 the rate of thiazolidine ring opening is competitive with hydrolysis of the ester function.The deuterium solvent kinetic isotope effect on the ring closure reaction is 7.5.
- Davis, Andrew M.,Layland, Nicola J.,Page, Michael I.,Martin, Frances,O'Ferrall, Rory More
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- Comparison of the electrospray ionization (ESI) responses of penicillins with ESI responses of their methanolysis products
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The electrospray ionization (ESI) responses, defined as the area of chromatographic peak of ion [M+H]+ obtained upon HPLC/ESI-MS analysis, of three β-lactam antibiotics, namely penicillin G, ampicillin and carbenicillin have been compared with
- Podniesińska, Lidia,Frański, Rafa?,Frańska, Magdalena
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- Alcohol-catalysed Hydrolysis of Benzylpenicillin
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The hydrolysis of benzylpenicillin is catalysed by alkoxide ions and other oxygen bases.Catalysis occurs by a nucleophilic pathway and the intermediate ester can be detected in some cases.The Broensted βnuc for alkoxide ions is 0.97, and is compatible with rate-limiting ring opening of the β-lactam.A solvent isotope effect of 3.2 for the trifluoroethanol-catalysed reaction suggests protonation by water occurs to the departing β-lactam nitrogen.Penicillin in not a particularly effective acylating agent of alcohols.
- Davis, Andrew M.,Proctor, Philip,Page, Michael I.
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p. 1213 - 1217
(2007/10/02)
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- Thiazolidine Ring Opening in Penicillin Derivatives. Part 1. Imine Formation
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The rate of epimerisation of (3S,5R,6R)-benzylpenicilloic acid at C-5 shows three distinct dependencies upon pH in aqueous solution.Below pH 6 the rate shows a sigmoidal dependence upon pH, whereas it is pH-independent between pH 6 and 12, and above pH 12 the rate is hydroxide-ion dependent.These different regions of pH dependence are interpreted in terms of three mechanistic pathways all of which involve opening the thiazolidine ring by C-S bond fission and re-closure to generate the epimer.At low pH the reaction occurs by unimolecular ring opening of the S-conjugate acid which is kinetically equivalent to the N-conjugate acid of pKa 5.14.The pH-independent pathway involves formation of a zwitterion by unimolecular opening of the neutral thiazolidine.At high pH the unprotonated imine intermediate is formed by concerted hydroxide-ion-catalysed ring opening.The mono- and di-methyl esters of benzylpenicilloate also epimerise at C-5.At low pH the rates are similar for all three compounds but above pH 6 the mono- and di-esters are, respectively, 21 and 1700 times less reactive than the dianion of the diacid.
- Davis, Andrew M.,Jones, Mark,Page, Michael I.
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p. 1219 - 1223
(2007/10/02)
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