Epoxidation of the stilbene double bond, a major pathway in aminostilbene metabolism

1. The vicinal diol 1-(4-acetylamino)-phenyl-2-phenyl-1,2-ethanediol is shown to be a major metabolite of cis- and trans-4-dimethylaminostilbene in the rat. 2. The threo-diastereomeric diols were identified in urine with both the cis- and trans-aminostilbene. This is consistent with enzymic trans-opening of an epoxide intermediate only for the cis-stilbene. For the hydrolysis of the trans-stilbene epoxide alternative mechanisms are discussed. 3. A mercapturic acid isolated from urine is identical with the reaction product of 4-acetylaminostilbene epoxide and N-acetylcysteine. This provides additional evidence for an epoxide intermediate. 4. Oxidation of the intercyclic linkage occurs also in 4-dimethylaminobibenzyl, leading to 1-phenyl-2-(4-acetylamino)-phenyl-1-ethanol as a major urinary metabolite. 5. The syntheses of several reference compounds, including the epoxides and dihydrodiols of cis- and trans-4-acetylaminostilbene are described.