Acid-catalyzed hydrolysis of α-ketoglutaramic acid : A proposed mechanism involving decarboxylation and amide hydrolysis of the γ-lactam, 2-pyrrolidone-5-hydroxy-5-carboxylic acid

The rates of the acid-catalyzed decarboxylation and amide hydrolysis of α-ketoglutaramic acid, the keto analog of glutamine, were investigated and the products of the reactions were characterized. In strong acid at 100°C, amide hydrolysis and decarboxylation occur with about equal facility, yielding α-ketoglutaric acid and 5-hydroxy-2-pyrrolidone, respectively. 5-Hydroxy-2-pyrrolidone undergoes further amide hydrolysis so that the products of complete acid hydrolysis of α-ketoglutaramic acid are ammonia (100%), carbon dioxide (50%), and approximately equal yields (50%) of α-ketoglutaric acid and succinic semialdehyde (β-formylpropionic acid). At increasing pH values, the relative rate of decarboxylation to amide hydrolysis of α-ketoglutaramic acid increases, such that, at pH values of 2 or greater, decarboxylation occurs almost exclusively. The decarboxylation product 5-hydroxy-2-pyrrolidone, was characterized chromatographically and by its infrared and pmr spectra; the compound may be regarded as the cyclized form of succinamic semialdehyde. A mechanism for the competing amide hydrolysis and decarboxylation reactions is proposed, and the potential biological significance of the decarboxylation pathway is discussed.