LARGE-SCALE SYNTHESIS OF THE CATECHOL METABOLITES OF DIETHYLSTILBESTROL AND HEXESTROL

Diethylstilbestrol (DES) and hexestrol (HES) are carcinogenic syntheti c estrogens. The major metabolites of these compounds are their catech ol derivatives, 3'-OH-DES and 3'-OH-HES. Oxidation of these metabolite s leads to the electrophilic quinones, which are presumably involved i n the tumor-initiating process. A synthetic route based on the McMurry coupling reaction was developed for the synthesis of 3'-OH-DES. Using commercially inexpensive starting materials, this compound was synthe sized in four steps, and the cis and trans isomers were separated and identified. Following the same synthetic route, 3'-OH-HES was synthesi zed in five steps.