Synthesis of (2R,3R)-erythro- and (2R,3S)-threo-fluoromalate using malic dehydrogenase; Stereoselectivity of malic dehydrogenase

3-Fluorooxalacetate is a substrate for malic dehydrogenase. When enzymatic reduction is slower than the rate of epimerization of the two enantiomers, only (2R,3R)-erythro-fluoromalate is formed. Conversely, when a high enzyme level and excess of NADH lead to reduction that is fast relative to the ep imerization rate, equal amounts of (2R,3R)-erythro- and (2R,3S)-threo-fluor omalate are formed. These data suggest that the V/K value for reduction of the R enantiomer to give the erythro isomer is similar to 100 times greater than for reduction of the S enantiomer to give the three isomer. The equil ibrium constant for the oxidation of fluoromalate is an order of magnitude less favorable than for oxidation of malate, while the equilibrium deuteriu m isotope effect from deuteration at C-2 of the substrate is 1.09 for fluor omalate versus 1.18 for malate. These effects reflect the inductive effect of fluorine at the 3-position.