Investigation on the chemoenzymatic synthesis of threo- and erythro-β-hydroxy-l-glutamic acid derivatives

Abstract

► Transformation of a malonic semialdehyde derivative in β-hydroxy glutamate precursors by aldolase. ► Separation of the two epimers by lipase PS. ► Assignment of configurations by Kazslauskas’ model and H-2 and H-3 chemical shifts. ► Possibility of transforming the products into β-hydroxy glutamic acid derivatives. A derivative of the malonic semialdehyde was transformed by means of a bioconversion catalyzed by the enzyme l -threonine aldolase from E. coli into a 6:4 epimeric mixture of two precursors of β-hydroxy glutamic acid. The enzyme was selective for the formation of the ( S )-configuration at C-2, whereas the configuration at C-3 was not controlled. The two epimers were separated exploiting a diastereoselective acylation in organic solvent catalyzed by lipase PS. The relative and absolute configurations of the products were preliminarily assigned on the base of the model proposed by Kazslauskas for the stereopreference of lipase PS and by comparison of the chemical shifts of the H-2 and H-3 protons of the two homologues. The possibility of transforming the obtained products into β-hydroxy glutamic acid derivatives by conventional chemical reactions was demonstrated.