Hormones estrone

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). 

Figure 23.9 This Robinson annulation reaction is used in the commercial synthesis of the steroid hormone estrone. The nucleophilic donor is a /3-diketone.

The sex hormone estrone has been synthesized by a route that involves the following step. Identify the pericyclic reactions involved, and propose a mechanism. 

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... 

In Australia, lambing in sheep has dropped to as little as 30% after grazing on subterranean clover. Trifolium subterraneum. The clover contains the isoflavonoids formononetin and genistein (Fig. 11.11). These compounds mimic the steroidal nucleus of the natural female hormone estrone. Alfalfa, M. sativa, and ladino clover. Trifolium repens, contain the even more potent isoflavonoid coumestrol. It is 30 times more active than genistein or formononetin, but occurs in lower concentrations in the plant (Shutt, 1976). 

T amaga wa Y, Yamaki R, Hirai H et al (2006) Removal of estrogenic activity of natural steroidal hormone estrone by ligninolytic enzymes from white rot fungi. Chemosphere 65 97-101... 

Draw a stepwise mechanism for the following intramolecular reaction, which is used in the synthesis of the female sex hormone estrone. 

Many compounds isolated from natural sources are aromatic in part. In addition to benzene, benzaldehyde, and toluene, such compounds as the steroidal hormone estrone and the well-known analgesic morphine have aromatic rings. Many synthetic drugs are also aromatic in part the tranquilizer diazepam (Valium) is an example. 

Doisy and his associates isolated the sex hormones estrone (1929), estriol (1930), and estradiol (1935). He also isolated two forms of vitamin K and synthesized it in 1936-39. For his work on vitamin K, Doisy was... 

Simple pi bonds are usually not good enough nucleophiles to react with polarized multiple bonds. If a Br0nsted acid or a Lewis acid is added to improve the electron sink, then addition can occur via the lone-pair-stabilized carbocation as the sink. Figure 8.7 shows a mechanistic example from a short synthesis of the human hormone estrone. 

As another biological example, a H-H bonding interaction was found in the electron density of the hormone estrone at its optimised geometry (B3LYP/... 

Figure 13 (see color section). Example of a H-H bond path in biological molecules. The chemical structure and the molecular graph of the hormone estrone (the blue arrow indicates the H-H bond path) (adapted from Ref. [133]). 

Estrogens. The biosynthetic relationship of the ovarian female sex hormones to androstenedione (their precursor), to cholesterol, and to each other is outlined in Figure 14-6. Estrone [3-hydroxy-l,3,5(10)-estratriene-17-one] was the first sex hormone to be isolated (Doisy et al., 1930 Butenand, 1930). Estradiol, which has been established as the true female sex hormone, is about 10 times more potent than estrone. It was not isolated for five years and took the extraction of 4 tons of sow ovaries to produce a little more than 10 mg of the hormone. Estrone was initially isolated from human pregnancy urine. 

The classical work of Butenandt and Doisy on the isolation of the estrognic hormone, estrone in 1929 from pregnancy urine was aided by much preliminary biological work, the introduction of important bioassay methods by Allen and Doisy in 1923 and Ascheim and Zondek and the involvement of the company Sobering AG. The structure was elucidated through the work of several different groups on the synthesis of numerous degradation products. Estrone and its derivatives from such natural sources were soon introduced into therapy. The first synthesis of a steroid, namely the naphthalenic relative equilenin (3)... 

The syntheses of tt-complexes of a hormone, estron chromium tri-carbonyl, and a provitamin D, ergosterol, and vitamin A are reported. 

Today, the association of aromaticity with fragrance has long been lost, and we now nse the word aromatic to refer to the class of compounds that contain six-membered benzene-like rings with three double bonds. Many naturally occurring compounds are aromatic in part, such as the steroidal hormone estrone and the analgesic morphine. In addition, many synthetic drugs are aromatic in part, such as the antidepressant fluoxetine (Prozac). Benzene itself has been found to cause bone marrow depression and consequent leukopenia, or lowered white blood cell count, on prolonged... 

Look at the following structure of the female hormone estrone, and tell whether each of the two indicated ring-fusions iscisortrans. 

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