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

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Abstract
The degradation of potassium clavulanate [having antibacterial properties] in a weakly alkaline aqueous solution was 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 NMR spectroscopy. High-performanc liquid chromatographic analysis of the reaction solution indicated that the reaction at 60.degree. C yielded at 4 pyrazine derivatives; II was not formed at 35.degree. C and III was not formed at 100.degree. C. A reaction mechanism is proposed which involves 4-amino-3-oxobutanol (IX) as a key intermediate.