Studies on clavulanic acid. Part 1. Stability of clavulanic acid in aqueous solutions of amines containing hydroxy groups

Abstract

The kinetics of the decomposition of clavulanate ion, (Z)-(2R,5R)-3-(2-hydroxyethylidene)-7-oxo4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate, in aqueous solutions of 2-amino-2-methylpropane1,3-diol, 2-amino-2-methylpropan-1-ol, 2-methoxyethylamine, 2,2,2-trifluorethylamine, and aminoacetonitrile have been studied. All reactions were conducted at 35.0 °C and 0.5M-ionic strength. In the pH range 8.05–9.80 the reaction is pseudo-first-order with respect to the concentration of clavulanate ion. The, aminolysis rate constants can be expressed as a sum of the terms representing the uncatalysed or water-catalysed amine reaction, the self-assisted nucleophilic reaction, and the hydroxide-ion-catalysed nucleophilic attack of amine on the β-lactam moiety.