A-Estradiol

Hydroxy ketones and hydroxy-a,/3-unsaturated ketones in the steroids such as estrone and testosterone, respectively, can be reduced to diols biochemically. Estrone acetate gave 68% yield of a-estradiol on incubation with baker s yeast at room temperature after five days [909]. Testosterone was reduced by bacteria to the saturated hydroxy ketones, etiocholan-17-ol-3-one and androstan-17-ol-3-one, and further to the diols, ep/-etiocholane-3,17-diol and the epimeric isoandrostane-3,17-diol, both in low yields [329]. 

Figure 7.6 Typical SFC separation of chlordiazepoxide (1), estrone (2), a-estradiol (3), /3-estradiol (4), equilin (S), and rf-equilenin (6) on a SB-cyanopropyl-50 column. (From Ref. 4.)...

The SFC separation of selected estrogens (estrone, equilin, a-estradiol, /3-estradiol, and d-equilenin) was achieved on a SB-cyanopropyl-50 capillary column using a carbon dioxide density gradient at an oven temperature of 73°C [5]. A typical analysis time on the 7-m column was 21... 

Double dehydrogenation and even complete aiomatization of the A-ring of 34iydroxy or 3-keto steroids can also be etiected the latter is of special interest in the preparation of estrogens, for example the conversion of the diene (60) to the a-estradiol derivative (61 equation 19) by Proactinomyces glob-erulaP ... 

Figure 42. Comparison of MIKE spectra of ions m/z 270, 111 and 288 produced in El from mixture of estrone (a), estradiol (b) and estriol (c) (as reflected spectra) with the same respective ions formed for authentic samples of these compounds [196].

P-Estradiol (previously known as a-estradiol) is purified by chromatography on Si02 (toluene/EtOAc 4 1) and recrystallised from CHCl3/hexane or 80% EtOH. It is stable in air, is insoluble in H2O, and is precipitated by digitonin. The UV has at 225 and 280 nm. The diacetate [3434-88-6] has m 97-98° and forms leaflets from aqueous EtOH. The 3-benzoate [50-50-0] crystallises from aqueous MeOH with m 193° and [a] +58° to... 

Estrogenic activity in mammals is mediated by several estranes. A good number of these compounds are better known by their trivial as opposed to systematic names. The estrane nucleus is fairly similar to a gonane in that the double bonds in ring A are actually enumerated. Structure 4-1 (Scheme 4) thus becomes estra-l,3,5-trien-17-one. This steroid is far better known as estrone. Its reduced counterpart 4-2 is named estra-l,3,5-triene-3,17/3-diol. The more prevalent name for this compound is estradiol or, somewhat less commonly, /3-estradiol, The isomer with the hydroxyl group below the plane of the paper is named estra-l,3,5-trien-17a-ol or a-estradiol. The systematic name for the methyl ether of estradiol becomes 3-methoxyestra-l,3,5-trien-17/3-ol. The product 4-4 from alkylation at position 17 can be named 17)8-methylestra-l,3,5-trien-17a-ol. That compound is also known as equilin, a name derived from the fact that it was first isolated from horse urine. An additional double bond as in 4-5 is simply added to three already present, thus estra-... 

Preparation of the corresponding cA-16a,17a-diol relies on the known propensity of many inorganic oxidizing agents to produce cA-diols. The sequence for synthesizing that isomer starts with heat-induced elimination of the elements of benzoic acid from estradiol 17-benzoate. The resulting 16-dehydro compound, 31-2, is then treated with osmium tetraoxide (Scheme 3.31). The stereochemistry of that transformation can be rationalized by positing the intermediacy of a complex such as that depicted in 31-3. The overall result is the formation of the c -diol 16a-hydroxy-a-estradiol (31-4). 

Retention time 4 (estrone), 4 (equilin), 4 (equilenin), 12.5 (a-estradiol), 15 (a-dihydroe-quilin), 16 (a-dihydroequilenin), 18 (p-estradiol), 19.5 (p-dihydroequilin), 22 (p-dihydroe-quilenin)... 

---