STEREOSPECIFICITY IN METABOLISM OF CHIRAL ISOMERS OF FONOFOS BY MOUSE-LIVER MICROSOMAL MIXED-FUNCTION OXIDASE

The P = S to P = O activation reaction mediated by mouse liver microsomal oxidase proceeds predominantly with retention of configuration. The stereochemical course of the reaction is consistent with the mechanism proposed by Ptashne et al. for the oxidative desulfuration of parathion to paraoxon in which initial attack by O2 on the thiono sulfur is postulated. Although retention of configuration remains the principal course of the oxidative desulfuration reaction, inversion also evidently occurs to a significant extent (20-30%). Inversion probably proceeds with initial attack of O2 on the P atom, followed by elimination of S. In this regard, the stereochemical course of peroxy acid oxidation of a chiral phosphinothioate ester to the corresponding oxon is reported to be dependent on the nature of the peroxy acid and acidity of the reaction medium, with inversion occurring in the presence of strong acids.