Synthesis and relative stereochemistry of the benzylic thioether diastereoisomers formed from glutathione and styrene oxide

Abstract The chemical reaction between (±) styrene oxide and glutathione produces both the benzylic and primary thioether positional isomers as a mixture of diastereoisomers ( 2, 5 and 3, 6 ), with a preference for the benzylic thioether isomers (66 : 34). Synthesis of the styrene oxide-glutathione conjugates from either (+)- or (−)- styrene oxide produces both positional isomers as single diastereoisomers. The benzylic thioether isomers ( 2 and 5 ) were prepared from protected 2-bromo-2-phenylethanol ( 8 ) and glutathione and were separated using hplc. The relative stereochemistry of the benzylic thioether isomers was assigned on the basis of the established chemical correlation between the optically pure styrene oxides and their precursors, the mandelic acids, as well as considerations of the mechanism of ring opening of epoxides by sulfur nucleophiles. The availability of the single diastereoisomers of the benzylic thioether isomers and the styrene oxideglutathione conjugates enables investigations concerned with the influence of chirality on the biotransformation and excretion of these conjugates.