KINETIC ASPECTS OF THE ENANTIOSPECIFIC REDUCTION OF SODIUM 3-FLUOROPYRUVATE CATALYZED BY RABBIT MUSCLE L-LACTATE DEHYDROGENASE - PRODUCTIONOF HOMOCHIRAL (R)-3-FLUOROLACTIC ACID METHYL-ESTER

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 procedur e for the enantiospecific reduction of 3-fluoropyruvate catalyzed by t his enzyme in a laboratory preparative scale is described. NADH was us ed in catalytic concentration by utilizing a NADH in situ regeneration system consisting of the oxidation of cis-1,2-bis(hydroxymethyl)cyclo hexane (BHMC, 7) to chiral tone(+)-(1R,6S)-cis-8-oxabicyclo[4.3.0]nona n-7-one (8) catalyzed by horse liver alcohol dehydrogenase (HLADH). An alysis of the isolated product (100% conversion), after methylation, r evealed the presence of (R)-3-fluorolactic acid methyl ester as the un ique product that was obtained in 80% overall yield and ee > 99%. This compound represents an important chiral building block for the synthe sis of several products with biological and/or pharmacological activit y. (C) 1998 Elsevier Science B.V.