Further degradation products of cephalosporin C. Isolation and synthesis of 2-(4-amino-4-carboxybutyl)thiazole-4-carboxylic acid

Abstract

A mixture of acidic, neutral and basic products was formed when cephalosporin C was subjected to mild hydrolysis in hot dilute acid. Oxidation of the neutral material with silver oxide yielded an acidic product which behaved like authentic [sigma] -amino- [sigma] -carboxyvaleryglycine on paper chromatography or electrophoresis, and which gave [alpha]-aminoadipic acid and glycine on hydrolysis with N-HC1 at 110[degree]. [sigma] -Amino-[sigma]-carboxyvaleryglycine had previously been obtained from cephalosporin N [(D-4-amino-4-carboxybutyl)penicillin] under similar conditions. An acidic compound, formed when cephalosporin C was kept in neutral aqueous solution at 37[degree], was isolated by chromatography on an anion-exchange resin. The physical and chemical properties of this compound, including its behavior on hydrogenolysis, suggested that it was 2-(D-4-amino-4-carboxybutyl)thiazole-4-carboxylic acid. The compound was racemized by treatment with acetic anhydride in aqueous solution. 2-(DL-4-Amino-4-carboxybutyl)thiazole-4-carboxylic acid was synthesized from methyl bromopyruvate and either 5,5-diethoxycarbonyl-5-phthalimidovalerothioamide or the corresponding acetamido compound, the thioamides being prepared from the corresponding nitriles. The synthetic compound was identical with the racemized product from cephalosporin C.