Kinetic studies of pyridoxal and pyridoxal-metal ion catalyzed dealdolation of novel [beta]-hydroxy amino acid model systems

Abstract

The rates of dealdolation of pyridoxal and pyridoxal-metal ion catalyzed [beta]-hydroxy amino acid model systems have been determined by proton nmr. The reaction rate is enhanced by the presence of electron donating groups at the beta carbon of the amino acid moiety or by the presence of a phenyl group at this position. [beta]-Hydroxyvaline, with two methyl groups at the beta carbon, undergoes dealdolation more readily than threonine, which has only one methyl group at the beta carbon. Serine which has no electron donating group at the beta carbon does not undergo dealdolation under the reaction conditions employed. A number of para substituted phenylserines were studied and the rate constants for dealdolation were determined. The amino acid having the most effective electron withdrawing substituent enhances the dealdolation rate to the greatest extent. In these substituted phenylserines [beta]-elimination and dealdolation were found to occur as parallel reactions. The metal ion-pyridoxal catalyzed systems undergo dealdolation more readily than the corresponding metal-free pyridoxal systems. This behavior is due to the fact that the electropositve center of the metal ion aids in attracting electrons toward the azomethine nitrogen. This electron shift facilitates rate-determining fission of covalent bonds at the alpha carbon atom of the amino acid. The observed rates in the metal-free systems are found to be the sum of the individual rates of the various reactive Schiff base species differing only in their degrees of protonation. The specific rate constants of the individual ionic species were determined for the [beta]-hydroxyvaline -pyridoxal Schiff base systems and the phenylthreonine-pyridoxal Schiff base systems.