Chemoenzymatic resolution of rac-malathion

Malathion, diethyl 2-[(dimethoxyphosphorothioyl)sulfanyl]butanedioate, is an organophosphate used to control insect pests. Malathion contains a diethyl succinate moiety that is a known functional group susceptible to desymmetrizing enzymes such as esterases that selectively react with a single enantiomer. Purified rac-malathion was subjected to hydrolysis at the diethyl succinate moiety of malathion under various conditions using wild type pig liver esterase to form (S)-malathion (12% ee) and ∼3:2 mixture of α- and β-monoacids of (R)-malathion. Technical malathion could not be enriched due to the presence of esterase inhibitors. Further investigation of this resolution using a panel of six PLE isoenzymes also demonstrated the formation of (S)-malathion, however, an improvement of up to 56% ee was obtained.

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S-(S)-Di(ethoyxcarbonyl)ethyl O,O-dimethyl phosphorodithioateC10H19O6PS2[α]D27=-80.0 (c 1.25, CHCl3)Source of chirality: (S)-malic acidAbsolute stereochemistry: (1S)