- Chemical reactivity of penicillins and cephalosporins. Intramolecular involvement of the acyl-amido side chain
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The rate of degradation of 6-epi-ampicillin in acidic, neutral, and alkaline aqueous solutions was followed at 35 °C and an ionic strength of 0.5 mol dm-3 (KCl) by high-performance liquid chromatography (HPLC) and spectrophotometric assays. Pseudo-first-order rate constants were determined in a variety of buffer solutions, and the overall pH-rate profile was obtained by extrapolation to zero buffer concentration. The hydrolysis of 6- epi-ampicillin is subject to acid and hydroxide-ion catalysis and, for a penicillin, an unusual pH-independent reaction. Intramolecular general base- catalyzed hydrolysis by the side chain amido group is proposed to explain the enhanced rate of neutral hydrolysis of 6-epi-ampicillin and cephalosporins. The β-lactam of 6-epi-ampicillin also undergoes intramolecular aminolysis by nucleophilic attack of the 6-α side chain amino group to give a stable piperazine-2,5-dione derivative. The low effective molarity for intramolecular aminolysis of only 40 M is partly attributed to the unfavorable trans to cis isomerization about the 6-amide side chain required for ring closure. Theoretical calculations show that the intramolecular aminolysis of 6-epi-ampicillin nucleophilic attack occurs from the α-face of the β-lactam ring with an activation energy of 14.4 kcal/mol.
- Llinas, Antonio,Vilanova, Bartolome,Frau, Juan,Munoz, Francisco,Donoso, Josefa,Page, Michael I.
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p. 9052 - 9060
(2007/10/03)
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- Preparation of some potential impurities of ampicillin and amoxicillin
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The preparation and characterization is described of some potential impurities of the penicillins ampicillin and amoxicillin, which have not been reported previously.These impurities may be formed during the semi-synthetic preparation of these antibiotics
- Yongxin, Zhu,Roets, Eugene,Busson, Roger,Janssen, Gerard,Hoogmartens, Jos
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