Enantiomers of isoprothiolane sulfoxide (diisopropyl 1-oxo-l, 3-dithiolan-2-ylidenemalonate) were resolved and separately analyzed both by chiral HPLC. The specific rotation was around + and-112° for each antipode. Isoprothiolane (diisopropyl l, 3-dithiolan-2ylidenemalonate) was easily oxidized by a rat liver 9000 g supernatant to produce its racemic sulfoxide, in which NADPH was an effective cofactor but NADH was not. The liver microsomes, however, preferentially formed its (+)-isomer in an enantiomeric excess of 38-43%. Phenobarbital (PB) increased the sulfoxidation activity of microsomes by 400% without any marked change in the enantiomeric excess. 3-Methylcholanthrene (3-MC) induced the microsomal activity more enantiomerically, forming isoprothiolane (+)-sulfoxide in an enantiomeric excess of 83%. Thus, 3-MC-induced microsomal enzyme(s) oxidize isoprothiolane to its (+)-sulfoxide more stereoselectively than PB-induced microsomal enzyme(s). The sulfoxidation of isoprothiolane by rice plants proceeded too slowly for the metabolite chirality to be analyzed. Both isoprothiolane (+)-and (-)-sulfoxides underwent rapid racemization by rat liver cytosol (105, 000 g supernatant) or rice plants, accompanied by the reduction to isoprothiolane.
All dialkyl 1,3-dithiolan-2-ylidenemalonates examined are considerably stable in rice plants, showing their t1/2 of 2.0-3.8 days. A non-cyclic analog with the t1/2 of 0.8 day, however, is rapidly metabolized probably through the oxidation at its thioether groups. Although the rat liver homogenate has both oxidation and hydrolysis activities, it shows predominantly the esterase activity in the absence of NADPH. In the rat liver homogenate, again, the non-cyclic analog is much more susceptible to oxidative metabolism in the presence of NADPH than, but as stable against the ester hydrolysis as the cyclic counterparts. The ester hydrolysis rates of the compounds well relate to the branching(s) at the ce-position or the resulting electronic (o*) or steric (ECS) effects of alcoholic alkyl groups.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.