17a-Ethynylestradiol

Acetylene and Potassium in Liquid Ammonia Potassium (40 g) is dissolved in 1 liter of dry liquid ammonia. Dry acetylene is then bubbled into the solution until the blue color is discharged. A solution of 15 g of estrone in 300 ml of dioxane is prepared and diluted with 300 ml of ether, cooled, and added to the potassium acetylide solution over a period of 10 min. The liquid ammonia is allowed to evaporate, an additional 500 ml of ether is added, and the mixture is allowed to stand overnight. About 3 liters of 5 % sulfuric acid is added and the organic layer separated. The water layer is re-extracted with fresh ether, and the combined ether extracts are washed twice with 5 % sodium carbonate solution, th6n several times with water, and finally evaporated under reduced pressure. The residue is dissolved in 150 ml of methanol, then an equal quantity of hot water is added and the mixture cooled. The precipitated solid is collected, washed with cold 60 % methanol and crystallized once from methanol-water to give 14.8 g (85%) of 17a-ethynylestradiol mp 143-144°. 

Chemical Name 3-methoxy-19-nor-17a-pregna-1,3,5( 10)-trien-20-yn-17-ol Common Name 17a-ethynylestradiol 3-methyl ether Structural Formula ... 

Effective removal of the estrogens 17 3-estradiol, estrone, and 17a-ethynylestradiol has been achieved using ozone under conditions that simulated those used for water treatment (Deborde et al. 2005). Analysis of the products showed the occurrence of two reactions ... 

Analogous reactions were postulated to occur for 17a-ethynylestradiol and, on the basis of experiments with model compounds, oxidation of the ethynyl group to -COCHO (Huber et al. 2004). 

Figure 7.7 Separation of ethynyl estrogens on silica gel 60 HPTLC plates using two 15-min developments in the solvent system hexane-chloroform-carbon tetrachloride-ethanol (7 18 22 1 v/v). Identification O methyl green (lane marker) 1 17a-ethynylestradiol ...

Acetoxy-20-keto-17a-pregnanes via Acetylenic Carbinols.165 A mixture of 1.9 g of 17a-ethynylestradiol diacetate, 2.1 g of A-bromoacetamide, 2 g of anhydrous sodium acetate, 10 ml of water and 100 ml of acetic acid is left at... 

Common Name lip-Methoxy-17a-ethynylestradiol Structural Formula ... 

Li AP, Hartman NR, Lu C et al. (1999) Effects of cytochrome P450 inducers on 17a-Ethynylestradiol (EE2) conjugation by primary human hepatocytes. British Journal of Clinical Pharmacology 48 733-742... 

The preparation of 17a-ethynyl-l 0/1,17/ -dihydroxyestr-4-en-3-one (5) was achieved by transformation of 17a-ethynylestradiol-17/f (3) with the fungus Aspergillus flavus190-191 17 a-ethynyl-19-nortestosterone (norethisterone, 4) was observed as an intermediate. 

Fragmentation reactions.1 Silver carbonate on Celite (Fetizon s reagent) quantitatively cleaves steroidal 17-ethynyl alcohols. Thus treatment of 17a-ethynylestradiol methyl ether (1) with silver carbonate on Celite in toluene under reflux gives estrone methyl ether (2) in quantitative yield. In the same way, dehydroepiandrosterone (4) was obtained from (3). 0H 0... 

Guengerich, F.P. (1988) Oxidation of 17a-ethynylestradiol by human liver cytochrome P-450. Molecular Pharmacology, 33, 500-508. 

The totally synthetic (i)-8a-r-isomer 28 of 178-hydroxy-17a-ethynylestr-5(10)-en-3-one (29) is about one-half as active as 29 in a pituitary blockage test . l-Acetoxy-17a-ethynylestradiol 3-acetate (30) is ten times as active orally as 17a-ethynylestradiol (31). ... 

In the above cases, the effects have been discussed only in terms of altered bioavailability that is, with increased clearance of 17a-ethynylestradiol, unexpected menstruation and pregnancies have resulted Some of the drug interaction... 

The oral contraceptive 17a-ethynylestradiol is a mechanism-based inactivator of P450 2B6 and modifies the (apo)protein , but the in vivo relevance of the inhibition has not been established. 

Subsequently, studies with microsomes, antibodies, and purified P450 3A4 quickly indicated that nifedipine was not the only substrate other substrates included other dihydropyridines , steroids quinidine , the oral contraceptive 17a-ethynylestradiol , and the carcinogen afla-toxin B, (ref [714]). With more studies and the application of recombinant systems, the repertoire of substrates expanded rapidly . 

Oral contraceptives contain acetylenes and can be mechanistic inactivators of P450 3A4. Inactivation has been demonstrated for 17a-ethynylestradiol, the major estrogenic component of oral contraceptives , and several of the progestogenic components, particularly... 

Lin, H.L., UM. Kent, and P.F. Hollenberg (2002). Mechanism-based inactivation of cytochrome P450 3A4 by 17a-ethynylestradiol Evidence for heme destruction and covalent binding to protein. J. Pharmacol. Exp. Then 301, 160-167. 

Yamamoto Y, Moore R, Hess H A, et al. (2006). Estrogen receptor a mediates 17a-ethynylestradiol causing hepatotoxicity. J. Biol. Chem. 281 16625-16631. 

Activated sludge mestranol 17a-ethynylestradiol 17/3-estradiol estrone [72]... 

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