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

Abstract

1. 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).

2. The formation of 3-(4′-hydroxyphenyl)-hex-2-en-4-one (VII) from diethylstilbestrol is the first reported example of a metabolic dearylation reaction.

3. The amount of cleavage products depends on the excess of H₂O₂ used.

4. The amount of H₂O₂ does not affect the extent of binding of diethylstilbestrol to DNA as mediated by peroxidases.

5. The syntheses of V, VI and VII are described.