Degradation of Clavulanic Acid in Aqueous Alkaline Solution : Isolation and Structural Investigation of Degradation Products

Abstract

The degradation of potassium clavulanate in a weakly alkaline aqueous solution has been investigated. Potassium clavulanate was degraded in 0.1 M Na2HPO4 solution at various temperatures. Four degradation products were isolated and their structures were elucidated as 2, 5-bis-(2-hydroxyethyl) pyrazine (I), 3-methyl-2, 5-bis-(2-hydroxyethyl) pyrazine (II), 3-(2-carboxyethyl)-2, 5-bis-(2-hydroxyethyl) pyrazine (III). and 3-ethyl-2.5-bis-(2-hydroxyethyl) pyrazine (IV) by mass spectroscopy and nuclear magnetic resonance spectroscopy. High-performance liquid chromatographic analysis of the reaction solution indicated that the reaction at 60°C yielded all four pyrazine derivatives, whereas II was not formed at 35°C and III was not formed at 100°C. A reaction mechanism is proposed which involves 4-amino-3-oxobutanol (IX) as a key intermediate.