Metabolism of polycyclic compounds. 20. The metabolism of phenanthrene in rabbits and rats: mercapturic acids and related compounds

Abstract

Both rabbits and rats dosed with phenanthrene excreted in urine the same stereoiso-meric form of N-acetyl-S-(9,10-dihydro-9-hydroxy-10-phenanthryl) cysteine. The non-acetylated cysteine derivative and a related conjugate which contained glycine but was not a derivative of 9-phenanthryl-cysteinylglycine were also excreted. The bile of these rats also contains the related cysteinylglycine and glutathione conjugates. Treatment of the mercapturic acid with mineral acid yielded phenanthrene and NN''-diacetylcystine together with small amounts of 9-phenanthryl-mercapturic acid, and hydrogenolysis with Raney nickel gave 9-hydroxy-phenanthrene. The related amino acid conjugates were decomposed in an analogous manner. N-Acetyl-S-(l,2-dihydro-2-hydroxy-l-phenan-thryl)cysteine, N-acetyl-S-(l,2-dihydro-l-hydroxy-2-phenanthryl) cysteine, N-acetyl-S-(3,4-dihydro-3-hydroxy-4-phenanthryl)cysteine and N-acetyl-S-(3,4-dihydro-4-hydroxy-3-phenanthryl)cysteine were probably also formed. These were decomposed by mineral acid to give phenanthrylmercapturic acids and hydroxyphenanthrenes. The syntheses of 1- and 9-phenanthrylcysteine and of their related mercapturic acids are described.