Large-scale synthesis of the catechol metabolites of diethylstilbestrol and hexestrol.
Diethylstilbestrol (DES) and hexestrol (HES) are carcinogenic synthetic estrogens. The major metabolites of these compounds are their catechol derivatives, 3'-OH-DES and 3'-OH-HES. Oxidation of these metabolites leads to the electrophilic quinones, which are presumably involved in 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 synthesized in four steps, and the cis and trans isomers were separated and identified. Following the same synthetic route, 3'-OH-HES was synthesized in five steps.
Jan
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Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 600 South 42nd Street, Omaha, Nebraska 68198-6805, USA.
Rogan
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Cavalieri
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D002396:Catechols / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004054:Diethylstilbestrol / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D045166:Estradiol Congeners / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D006589:Hexestrol / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry
D002396:Catechols; D045166:Estradiol Congeners; D006589:Hexestrol; D004054:Diethylstilbestrol