Kinetic aspects of the enantiospecific reduction of sodium 3-fluoropyruvate catalyzed by rabbit muscle l-lactate dehydrogenase: Production of homochiral ( R)-3-fluorolactic acid methyl ester

• Published in: Journal of molecular catalysis. B, Enzymatic Enzymatic, 1998-01, Vol.4 (1), p.67-76
• Main Authors: Gonçalves, Luciana P.B., Antunes, O.A.C., Pinto, Gerson F., Oestreicher, Enrique G.
• Format: Article
• Language: English
• Subjects: ( R)-3-fluorolactic acid methyl ester; Bioconversions. Hemisynthesis; Biological and medical sciences; Biotechnology; Chiral building block; Enantiospecific reduction; Enzyme kinetics; Fundamental and applied biological sciences. Psychology; l-lactate dehydrogenase; Methods. Procedures. Technologies
• ISSN: 1381-1177; 1873-3158
• DOI: 10.1016/S1381-1177(97)00023-4

In the present work the reduction of sodium 3-fluoropyruvate catalyzed by rabbit muscle l-lactate dehydrogenase ( l-LDH) was studied by means of initial rate experiments. Estimates of the limiting values of the kinetic parameters of the reaction were obtained. A kinetic mechanism involving a compulsory order of substrate binding to l-LDH, with NADH being the first substrate, is proposed. In addition, a simple procedure for the enantiospecific reduction of 3-fluoropyruvate catalyzed by this enzyme in a laboratory preparative scale is described. NADH was used in catalytic concentration by utilizing a NADH in situ regeneration system consisting of the oxidation of cis-1,2-bis(hydroxymethyl)cyclohexane (BHMC, 7) to chiral lactone (+)-(1 R, 6 S)- cis-8-oxabicyclo[4.3.0]nonan-7-one ( 8) catalyzed by horse liver alcohol dehydrogenase (HLADH). Analysis of the isolated product (100% conversion), after methylation, revealed the presence of ( R)-3-fluorolactic acid methyl ester as the unique product that was obtained in 80% overall yield and ee > 99%. This compound represents an important chiral building block for the synthesis of several products with biological and/or pharmacological activity.