Dearylation and other cleavage reactions of diethylstilbestrol: novel oxidative pathways mediated by peroxidases.

Oxidation of diethylstilbestrol (I) by peroxidases from horseradish or mouse uterus in the presence of H2O2 in vitro leads to Z,Z-dienestrol (II) and to a number of cleavage products, five of which were identified by g.l.c.-mass spectrometry and comparison with authentic reference compounds as 4-hydroxybenzoic acid (III), 4'-hydroxypropiophenone (IV), 1'(4'-hydroxyphenyl)-propan-1-on-2-ol (V), 1-(4'-hydroxyphenyl)-propan-1,2-dione (VI) and 3-(4'-hydroxyphenyl)-hex-2-en-4-one (VII). The formation of 3-(4'-hydroxyphenyl)-hex-2-en-4-one (VII) from diethylstilbestrol is the first reported example of a metabolic dearylation reaction. The amount of cleavage products depends on the excess of H2O2 used. The amount of H2O2 does not affect the extent of binding of diethylstilbestrol to DNA as mediated by peroxidases. The syntheses of V, VI and VII are described.