Synthesis and estrogenic properties of 17-epi-ethynylestradiol and its ether derivatives epimestranol and epiquinestrol.
The synthesis of 17-epi-ethynylestradiol (10), the 17 beta-ethynyl-17 alpha-ol epimer of the well-known orally active estrogen, ethynylestradiol (1), was achieved by LiA1H4 reduction of epoxide 9, as well as by demethylating epimestranol (11) with CH3MgI. Compound 11 was obtained by the unusual 17 beta-ethynylation of estrone 3-methyl ether 22 under equilibrating conditions. The in vitro estrogen receptor-binding affinity and the oral estrogenicity in the rat for the 17-epi compounds 10, 11 and 20 (epiquinestrol) was evaluated. Despite moderate estrogen receptor-binding affinity, compound 10 was devoid of measurable estrogenicity at 10 mg/kg or antiestrogenicity at 3 mg/kg.
D000818:Animals; D004965:Estrogen Antagonists / Q000138:chemical synthesis; D004997:Ethinyl Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008656:Mestranol / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D009651:Norpregnatrienes / Q000138:chemical synthesis*; D011800:Quinestrol / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism; D013237:Stereoisomerism; D014599:Uterus / Q000187:drug effects; D014621:Vagina / Q000187:drug effects
D004965:Estrogen Antagonists; D009651:Norpregnatrienes; D011960:Receptors, Estrogen; D004997:Ethinyl Estradiol; D008656:Mestranol; D011800:Quinestrol