SYNTHESIS OF MERCAPTURIC ACID-DERIVATIVES OF PUTATIVE TOXIC METABOLITES OF BROMOBENZENE

The synthesis and characterization of nine isomerically defined S-arylmercapturic acids of interest in connection withthe metabolism of the model hepatotoxin bromobenzene is described. Included are three S-(bromophenyl)-, two S-(bromohydroxyphenyl)-, and three S-(bromodihydroxyphenyl)mercapturic acids of defined substitution pattern. In addition, several related compounds with two or no bromine atoms are described. These syntheses depend on two basic methods, 1,4-addition of various arene thiols to acetamidoacrylic acid or the 1,4-addition of N-acetyl-L-cysteine to various benzoquinone derivatives. In addition, we describe a method for efficient conversion of the mercapturic acids to thioanisole derivatives, regioisomers of which can be separated and detected at low levels by capillary gas-liquid chromatography. © 1990, American Chemical Society. All rights reserved.