Dose-dependent stereoselectivity in the formation of mercapturic acids from cyclohexene oxide by the rat

Rats dosed with cyclohexene oxide excreted only two of the four possible isomeric N-acetyl-S-2-hydroxycyclohexyl-L-cysteines, the two diastereoisomers of N-acetyl-S-(trans-2-hydroxycyclohexyl)-L-cysteine. No trace of the corresponding two cis-2-hydroxy compounds was found by use of 1-HNMR, 13-CNMR, or GLC methods. A rapid and selective GLC method was developed to assay the ratio and concentrations of the two trans-mercapturic acids. Up to a dose of 0.5 mmol of cyclohexene oxide per rat, 21 +/- 4% of the dose was excreted as mercapturic acid. At higher doses the amount of mercapturic acid excreted remained constant, presumably because of the exhaustion of the glutathione supply in the body. The ratio of trans-diastereoisomers was found to vary from 6:1 at low doses to 3:1 at high dose, implying that the formation of mercapturic acids initially occurs with a high degree of stereoselectivity.