Estrogens intermediates

Today, a variety of therapeutic estrogens are produced semisynthetically from estrogen intermediates synthesized from diosgenin and other natural precursors. Two semisynthetic, orally active estrogens are ethinyl estradiol (5.27) and its 3-methyl ether (5.28, mestranol). Both of these are used in oral contraceptives (see section 5.8.3). Quinestrol (5.29) is another semisynthetic estrogen. The most important property of the semisynthetic estrogens is their increased oral effectiveness. 

The condensation of 6 methoxy-1-vinyl-l-tetralol with 2-ttifluoromethyl-l 3 cyclopentanedione in the presence of a small amount of triethylamine produces a secodione (equation 104) This dione is an intermediate in the total synthesis of 13-tnfluoromethyl estrogens, such as 18,18,18-tnfluoro 17(3 estradiol [121] Regwselecnve alkylation of a fluorinated (3-disulfone occurs at low tempera ture [122] (equation 105)... 

In vivo studies in animals suggest that endosulfan may disrupt normal reproductive hormone levels in male animals, but that it is not an endocrine disrupter in females. Persistent depressed testicular testosterone was seen in male rats after intermediate duration oral exposures to endosulfan. In ovariectomized female rats, orally administered endosulfan did not induce normal development of female reproductive tissues, and in female mice and immature female rats, acute parenteral exposure to endosulfan did not affect several endocrine-related end points. In vitro studies have evaluated endosulfan for estrogen receptor (ER) and cytosolic protein binding affinity, ER-mediated reporter gene expression, estrogenic induction of cell proliferation, and alteration of relative abundance of active estradiol metabolites. Overall, in vitro evidence in favor of endosulfan estrogenicity indicates relatively weak potency compared to 17[3-estradiol. Apparently contradictory results were reported in different... 

Nomiyama K, T Tanizaki, H Ishibashi, K Arizono, R Shinohara (2005) Production mechanism of hydroxylated PCBs by oxidative degradation of selected PCBs using TiOj in water and estrogenic activity of their intermediates. Environ Sci Technol 39 8762-8769. 

Tanghe T, W Dhooge, W Verstraete (2000) Formation of the metabolic intermediate 2,4,5-trimethyl-2-pentanol during incubation of a Sphingomonas sp. strain with the xeno-estrogenic octylphenol. Biodegradation 11 11-19. 

Reaction of estrone (2) with an excess of the lithium reagent from 3-iodofuran gives intermediate diol 3. The stereochemical assignment follows from the well-known propensity of steroids for attack from the less-hindered backside (a) of the molecule. Acylation of 3 with acetic anhydride then affords the estrogen estrvfurate (4).1... 

Navas JM, Gonzalez-Mazo E, Wenzel A, Gomez-Parra A, Segner H (1999) Linear alkylbenzene sulphonates and intermediate products from their degradation are not estrogenic. Mar Pollut Bull 38 880-884... 

Although the occurrence of the non-ionic surfactant nonylphenol ethoxylate (NPEO Fig. 6.7.1) and its biodegradation intermediates in the aquatic environment has attracted large interest [18] because of the potential of some biotransformation products to mimic estrogenic effects, their fate and distribution in soil environments has been only investigated in a few cases. 

It seems probable from our discussion that individual normal males, for example, vary through wide limits (possibly 10-fold or more) in their production of both androgens and estrogens. If we classify individual men roughly as (1) low, (2) intermediate, and (3) high producers of each of the two types of hormones, we find that an... 

It seems obvious that if one wishes to deal intelligently with problems of sex (which involve real people) we should take account of these variations and not think in terms of a population the members of which are "normal" or about average in estrogen and androgen production. The intermediate-intermediate group may be larger than any other, but it constitutes only one group out of nine possibilities and may conceivably include only those who have no acute sex problems. 

SMLs have been established for the monomers commonly used in making PET (Table 14.2). Studies conducted using monomers and PET intermediates indicated that these materials are essentially non-toxic and pose no threats to human health. The chemistry of compounds that are used to manufacture PET shows no evidence of estrogenic activity (International Life Sciences Institute, 2000). 

Fig. 6.8 Breakthrough curves for ligands infused through an estrogen receptor p FAC assay. Slow tight-binding ligands (nafoxidine and tamoxifen) exhibit diffuse breakthrough curves, while ligands with rapid kinetics exhibit sharper curves (norethindrone). Dehydroisoandro-sterone, a ligand intermediate between norethindrone and nafoxidine, was undetected in this experiment.

Though the preparation of the estrogen antagonist tamoxifen (9-3) appears to be comparable to the foregoing, the presence of the ethyl substituent on the ethylene has important stereochemical consequences. The sequence also differs from the foregoing by starting with an intermediate (9-1) that aheady includes both carbons of the... 

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