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Estrone, production

Estrone determinations are limited to diagnosis of postmenopausal bleeding and the menstrual dysfunction caused by extraglandular estrone production. Normally, blood estrone concentrations parallel estradiol concentrations throughout the menstrual cycle, but at slightly lower concentrations. For a specific analysis of estrone, the interested reader is directed to other references. ... [Pg.2136]

The ovarian granulosa cell, in response to stimulation by follicle-stimulating hormone (FSH) from the anterior pituitary gland and through the catalytic activity of P450 aromatase, converts testosterone to estradiol, the predominant and most potent of the ovarian estrogens (see Fig. 34.23). Similarly, androstenedione is converted to estrone in the ovary, although the major site of estrone production from androstenedione occurs in extraovarian tissues, principally skeletal muscle and adipose tissue. [Pg.648]

Estrogens are biosynthesized in the maturing dominant foiiicle and in the corpus luteum in premenopausal women. During pregnancy, the placenta becomes the primary location of estrogen biosynthesis (5,6). Approximately 50% of estrone production occurs in the ovaries. The remaining estrone is biosynthesized from estradiol as well as from the conversion of estrone sulfate to estrone in the adrenal gland and the aromatization of androstenedione. In contrast to premenopausal women, in whom the natural estrone to estradiol ratio is 1 2, postmenopausal women have an estrone to estradiol ratio of 2 1, which reflects the loss of ovarian function. [Pg.2065]

R B Woodward was one of the leading organic chemists of the middle part of the twenti eth century Known pnmanly for his achievements in the synthesis of complex natural products he was awarded the Nobel Pnze in chemistry in 1965 He entered Massachusetts Institute of Tech nology as a 16 year old freshman in 1933 and four years later was awarded the Ph D While a student there he earned out a synthesis of estrone a female sex hormone The early stages of Woodward s estrone synthesis required the conversion of m methoxybenzaldehyde to m methoxy benzyl cyanide which was accomplished in three steps... [Pg.662]

The two synthetic steroidal estrogens which have attained the greatest degree of therapeutic use are ethinyl estradiol [57-63-6] (EE) (5) and its 3-methyl ether, mestranol [72-33-3]((5). In contrast to the naturally occurring estrone derivatives, these acetylenic analogues are orally active and are the main estrogenic components of combination oral contraceptives (see Contraceptives) and certain estrogen replacement products. [Pg.231]

Under certain conditions surface catalytic deuterations can lead to the exchange of benzylic hydrogens. An example in the steroid field is the exchange of the benzylic hydrogens in estrone methyl ether (42) with deuterium in the presence of palladized charcoal." " According to mass spectrometric analysis, the product (43) contains three deuteriums (83 %), which have been assigned to the 6- and 9a-positions on the basis of NMR evidence." " ... [Pg.157]

The alkynylation of estrone methyl ether with the lithium, sodium and potassium derivatives of propargyl alcohol, 3-butyn-l-ol, and propargyl aldehyde diethyl acetal in pyridine and dioxane has been studied by Miller. Every combination of alkali metal and alkyne tried, but one, gives the 17a-alkylated products (65a), (65c) and (65d). The exception is alkynylation with the potassium derivative of propargyl aldehyde diethyl acetal in pyridine at room temperature, which produces a mixture of epimeric 17-(3, 3 -diethoxy-T-propynyl) derivatives. The rate of alkynylation of estrone methyl ether depends on the structure of the alkyne and proceeds in the order propar-gylaldehyde diethyl acetal > 3-butyn-l-ol > propargyl alcohol. The reactivity of the alkali metal salts is in the order potassium > sodium > lithium. [Pg.68]

Methoxy-cis-19-norpregna-l,3,5(10),17(20)-tetraene A solution of 31 g (109 mmolesi of estrone methyl ether in 600 ml of benzene is added rapidly to a solution of 469 mmoles of ethylidenetriphenylphosphorane in 1.2 liters of DMSO. After heating under nitrogen at 60° overnight, the reaction is cooled, poured into ice water, and extracted with three portions of hexane, backwashed with three portions of water and the hexane removed. The crude product, dissolved in petroleum ether (bp, 30-60°), is filtered through 225 g of alumina (activity I). The residue from the eluate consists of 95 % cis- and 5 % tran5-isomers, as determined by vpc analysis. After recrystallization from ether-methanol, 26.3 g (82%) of cw-isomer is obtained mp 76.5-77.5° [a]o 60°. [Pg.132]

Methoxy-D-Homo-estra-l,3,5(10)-trien-17a-one (96)" (/) Acetic acid (6.4 ml) is added to a stirred solution of estrone methyl ether (93 1.1 g) in ethanol (35 ml) containing potassium cyanide (6 g) at 0°. After being stirred for 1 hr at 0° and 2.5 hr at room temperature, the reactants dissolve and potassium acetate preciptates. Water (65 ml) is added to the reaction mixture and the precipitated solid is collected by filtration. The crude product is dissolved in ethyl acetate and the ethyl acetate solution is washed with water, dried over anhydrous magnesium sulfate and evaporated to dryness under reduced pressure. Recrystallization of a portion of the crude product from cyclohexane-acetone gives 3-methoxy-17a-cyano-estra-l, 3,5(10)-trien-17j5-ol (94a) as needles mp 158.5°. [Pg.388]

Although estrone and estradiol (26) have both been isolated from human urine, it has recently been shown that it is the latter that is the active compound that binds to the so-called estrogen receptor protein. Reduction of estrone with any of a large number of reducing agents (for example, any of the complex metal hydrides) leads cleanly to estradiol. This high degree of stereoselectivity to afford the product of attack at the alpha side of the molecule is characteristic of many reactions of steroids. [Pg.161]

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. [Pg.162]

In about 250 cc of liquid ammonia (cooled with dry ice and acetone) are dissolved about 7.5 g of potassium and into the solution acetylene is passed until the blue color has disappeared (about 3 hours). Then slowly a solution or suspension of 3 g of estrone in 150 cc of benzene and 50 cc of ether is added. The freezing mixture is removed, the whole allowed to stand for about 2 hours and the solution further stirred overnight. Thereupon the reaction solution is treated with ice and water, acidified with sulfuric acid to an acid reaction to Congo red and the solution extracted five times with ether. The combined ether extracts are washed twice with water, once with 5% sodium carbonate solution and again with water until the washing water is neutral. Then the ether is evaporated, the residue dissolved in a little methanol and diluted with water. The separated product is recrystallized from aqueous methanol. The yield amounts to 2.77 g. The 17-ethiny I-estradiol-3,17 thus obtained melts at 142°C to 144°C . [Pg.589]

The first step of the Robinson annulation is simply a Michael reaction. An enamine or an enolate ion from a jS-keto ester or /3-diketone effects a conjugate addition to an a-,/3-unsaturated ketone, yielding a 1,5-diketone. But as we saw in Section 23.6,1,5-diketones undergo intramolecular aldol condensation to yield cyclohexenones when treated with base. Thus, the final product contains a six-membered ring, and an annulation has been accomplished. An example occurs during the commercial synthesis of the steroid hormone estrone (figure 23.9). [Pg.899]

In this example, the /3-diketone 2-methyJ-l,3-cyclopentanedione is used to generate the enolate ion required for Michael reaction and an aryl-substituted a,/3-unsaturated ketone is used as the acceptor. Base-catalyzed Michael reaction between the two partners yields an intermediate triketone, which then cyclizes in an intramolecular aldol condensation to give a Robinson annulation product. Several further transformations are required to complete the synthesis of estrone. [Pg.899]

The homology of the tricyclic products in Scheme 6 to the ABC-ring portion of the steroid nucleus is obvious. In fact, the facility with which these tricyclic materials can be constructed from simple building blocks provided the impetus for the development of an exceedingly efficient synthesis of the female sex hormone, estrone (1). This important biomolecule has stimulated the development of numerous synthetic strategies and these have been amply reviewed.16 The remainder of this chapter is devoted to the brilliant synthesis of racemic estrone by K. P. C. Vollhardt et al.i2 17... [Pg.160]

The synthetic problem is now reduced to cyclopentanone 16. This substance possesses two stereocenters, one of which is quaternary, and its constitution permits a productive retrosynthetic maneuver. Retrosynthetic disassembly of 16 by cleavage of the indicated bond furnishes compounds 17 and 18 as potential precursors. In the synthetic direction, a diastereoselective alkylation of the thermodynamic (more substituted) enolate derived from 18 with alkyl iodide 17 could afford intermediate 16. While trimethylsilyl enol ether 18 could arise through silylation of the enolate oxygen produced by a Michael addition of a divinyl cuprate reagent to 2-methylcyclopentenone (19), iodide 17 can be traced to the simple and readily available building blocks 7 and 20. The application of this basic plan to a synthesis of racemic estrone [( >1] is described below. [Pg.162]

The total synthesis of ( )-estrone [( )-1 ] by Vollhardt et al. is a novel extension of transition metal mediated alkyne cyclotrimeriza-tion technology. This remarkable total synthesis is achieved in only five steps from 2-methylcyclopentenone (19) in an overall yield of 22%. The most striking maneuver in this synthesis is, of course, the construction of tetracycle 13 from the comparatively simple diyne 16 by combining cobalt-mediated and ort/io-quinodimethane cycloaddition reactions. This achievement bodes well for future applications of this chemistry to the total synthesis of other natural products. [Pg.165]

The strains described in Table 9.4 are all of commerdal value since they produce compounds which are either pharmacologically active or can be converted to pharmacologically important compounds. For example, the production of 1,4-androstadiene-3,17-dione from (5-sitosterol provides material which can be readily converted to estrone, while 4-androstene-3,l 7-dione can be converted to testosterone. [Pg.308]

The ceUular source of the various ovarian steroids has been difficult to unravel, but a transfer of substrates between two cell types is involved. Theca cells are the source of androstenedione and testosterone. These are converted by the aromatase enzyme in granulosa cells to estrone and estradiol, respectively. Progesterone, a precursor for all steroid hormones, is produced and secreted by the corpus luteum as an end-product hormone because these cells do not contain the enzymes necessary to convert progesterone ro other steroid hormones (Figure 42-8). [Pg.442]

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 ... [Pg.31]

Reduction of dienes incorporated into steroid structures may lead to different configurations in the products. For example, treatment of 8(9),14(15)-bisdehydroestrone 42 (R = H) for four hours at room temperature with twenty equivalents of trifluoroacetic acid and two equivalents of triethylsilane leads to an ionic hydrogenation product mixture containing the natural 8/1,9a,14a-estrone 43 as a minor component (11%) and the 8a,9/i, l 4/i-isomcr 44 as the major component (83%) (Eq. 92).241 The related methyl ether (42, R = Me) behaves in a similar fashion.241 The yield of natural isomer 46 formed from the methyl ether of A8(9),i4(i5)-bigdehydroestradiol analog 45 increases from 22 to 34%, and that of... [Pg.42]


See other pages where Estrone, production is mentioned: [Pg.881]    [Pg.1328]    [Pg.13]    [Pg.866]    [Pg.881]    [Pg.1328]    [Pg.13]    [Pg.866]    [Pg.210]    [Pg.242]    [Pg.242]    [Pg.243]    [Pg.243]    [Pg.417]    [Pg.430]    [Pg.10]    [Pg.38]    [Pg.51]    [Pg.307]    [Pg.450]    [Pg.442]    [Pg.87]    [Pg.159]    [Pg.160]    [Pg.167]    [Pg.160]    [Pg.302]    [Pg.218]    [Pg.544]    [Pg.31]    [Pg.260]    [Pg.134]   
See also in sourсe #XX -- [ Pg.236 ]




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