Estradiol analogs

Reaction of estrone with a metal acetylide affords 17a-ethynyl-173-hydroxy-estradiol (etbynylestradiol, 30a EE). This compound is equipotent with estradiol by subcutaneous administration, but it is 15 to 20 times as active when administered orally. Ethynylation of the methyl ether of estradiol analogously affords mestranol (30b), It should be noted that the same factors apply in these reactions as in previously discussed reductions at 17 almost the sole products of these reactions are those which result from attack of reagent from the least hindered a side of the steroid. Ethynylestradiol and mestranol are of special commercial significance since the majority of the oral contraceptives now on sale incorporate one or the other of the compounds as the estrogenic component. 

Interesting fluorinated estradiol analogs have been prepared from 4-fluoroestradiol (6), which is obtained from 19-nortestosterone (3) via fluorination of enamine 4 with perchloryl fluoride to give 4-fluoro-19-nortestosteronc (5), followed by selenium dioxide aromatization. ... 

Steroidal SERM-Type Antagonists Several steroidal ER antagonists have been described in the literature. It was established that attachment of a side-chain to the 11- or 7-position of 17(5E2 or 17P-ethinyl-estradiol converts the molecules from agonists into antagonists. Aventis Pharma (formerly Hoechst Marion Roussel) disclosed 17PE2 and 17P-ethinyl-estradiol analogs having a SERM-type BSC attached to the... 

Equally important is the high affinity binding of the Tc-estradiol analog to the estradiol receptor. The functional group chosen must not interfere with this binding and must be attached to the estradiol molecule at a point which does not interfere with binding to the receptor. The ability of the Tc-compound to... 

Isotope labeling by derivative formation with deuterated reagents is useful for the preparation of analogs such as dg-acetonides, da-acetates, da-methyl ethers, dg-methyl esters, etc. The required reagents are either commercially available or can be easily prepared. (The preparation of da-methyl iodide is described in section IX-F. Various procedures are reported in the literature for the preparation of dg-acetone, da-diazometh-ane57.i63.i73 and da-acetyl chloride. ) These reactions can be carried out under the usual conditions and they need no further discussion. A convenient procedure has been reported for the da-methylation of sterically hindered or hydrogen bonded phenolic hydroxyl functions by using da-methyl iodide and sodium hydroxide in dimethyl sulfoxide solution. This procedure should be equally applicable to the preparation of estradiol da-methyl ether derivatives. 

Isoflavones also have a diphenylpropane structure in which the B ring is located in the C3 position. They have structural analogies to estrogens, such as estradiol, with hydroxyl groups at the C7 and C4 positions (Shier and others 2001). 

An exactly analogous enzymic transformation is encountered during the formation of oestrogen and androgen sex hormones, e.g. estradiol and testosterone respectively, where dehydroepiandrosterone is oxidized to androstenedione. 

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