Preparation of 14,15-secoestra-1,3,5(10)-trien-15-ynes, inhibitors of estradiol dehydrogenase.
The conversion of estrone to 14,15-secoestratrien-15-ynes, inactivators of estradiol dehydrogenase from human term placenta, is described. The optically pure precursor 7-acetoxy-octahydro-2-phenanthrenecarboxylic acid methyl ester is prepared from estrone in five steps and 40% yield. The unsubstituted propargylic secoestratriene diol, a mechanism-based inactivator of estradiol dehydrogenase, and the corresponding acetylenic ketone, an affinity label inactivator of the same enzyme, arise from the phenanthrene ester in three and four steps. The propargylic secoestratriene diol also competes with [3H]estradiol for binding to calf uterus estrogen receptor and possesses weak uterotrophic activity.
Auchus
R J
RJ
Department of Pharmacology, Washington University School of Medicine, St. Louis, MO 63110.
Palmer
J O
JO
Carrell
H L
HL
Covey
D F
DF
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D055598:Chemical Phenomena; D002621:Chemistry; D003461:Crystallography; D004960:Estradiol Dehydrogenases / Q000037:antagonists & inhibitors*; D004963:Estrenes / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D006801:Humans; D009929:Organ Size; D010084:Oxidation-Reduction; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D011960:Receptors, Estrogen / Q000378:metabolism; D012632:Secosteroids / Q000138:chemical synthesis* / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects
D004963:Estrenes; D011960:Receptors, Estrogen; D012632:Secosteroids; C050965:14,15-secoestra-1,3,5(10)-trien-15-yne-3,17-diol; C056854:3-hydroxy-14,15-secoestra-1,3,5(10)-trien-15-yn-17-one; D015067:17-Hydroxysteroid Dehydrogenases; D004960:Estradiol Dehydrogenases