4-Androsten-17/?-ol-3-one

The early functional models for this oxidation chemistry were rather simple Udenfriend used iron(II), EDTA, ascorbic acid (as the reducing agent) and O2 to hydroxylate arenes, while Hamilton showed that the same system hydroxylates unactivated C—H bonds (e.g. androsten-3-ol-17-one is converted to androsten-3,7-diol-17-one). Mimoun developed the use of an iron(II)/PhNHNHPh/ H1CO2H/O2 system which is also active for alkane hydroxylation. Curiously, other metals [copperfll), manganese(II), vanadium(II), cobalt(II)] are also active. In the hydroxylation of arenes, an arene oxide is believed to be the intermediate in P-450 dependent systems, because a 1,2-shift of a proton in the arene, the NIH shift is often observed. Neither the Udenfriend nor Mimoun models show such a shift, however. 

Androsten-3/ -ol-17-one acetate is reduced over Raney nickel to the 17jS-alcohol, which is protected as a benzoate. This allows the selective hydrolysis of the acetate with methanolic sodium hydroxide solution. A final Oppenau-er oxidation leads to testosterone benzoate, hydrolysis of which gives the target compound. 

A soln. of Z i -androstene-3/ -ol-17-one acetate in the minimum amount of diloro-form distributed as a film on the inside walls of a large conical flask, which is then filled with oxygen, stirred 5 days at room temp, with addition of more chloroform to prevent crystallization of the startg. m. 14j5-hydroperoxy-zli5-androstene-3 -ol-17-one 3-monoacetate. Y 82%. A. Afonso, Can. J. Chem. 47, 3693 (1969). 

For the formation of testosterone (51), androsten-5-3-ol-17-one (50) obtained by oxidation from cholesterol was employed although it was also derivable from diosgenin by way of l6-dehydropregnenolone as described for the preparation of progesterone. The synthesis of the androgen followed the route shown and the acetate was isolated in an overall yield of nearly 40% in the Syntex procedure from the androstenone intermediate. 

Hydroxylation. Maume and Horning2 report that trimethylsilyl (TMSi) enol ethers of ketosteroids when irradiated with UV light (dibenzoyl peroxide can also be used) are converted into the trimethylsilyl derivative of an a-hydroxy ketone. Thus the TMSi enol ether of A5- mdrostene-3/3-ol-17-one (1) gives (2) as the chief reaction product. Similarly, A -androstene-3/3,17/3-diol-16-one is converted into... 

The Mexican owners of Syntex recruited after Marker s departure George Rosenkranz. Within two years, Rosenkranz succeeded not only in the large-scale production of progesterone, but he also estabhshed the synthesis of the male sex hormone, testosterone, from yam roots. The synthesis starts from 16-dehydro-pregnenolone acetate, which is converted into its oxime Beckmann rearrangement ofthe latter is followed by hydrolysis and yields 5-androsten-3)3-ol-17-one acetate. 

The double bond in 5-androsten-3jS-ol-17-one is first hydrogenated over paUadium/carbon. Androstan-3/ -ol-17-one is next oxidised with chromic acid, and the diketone selectively dibrominated in the A-ring. By a double elimination of HBr, androstadienedione is produced. Flash pyrolysis on quartz beadlets at 600 °C in tetralin or mineral oil gives then oestrone, which requires only hydrogenation to yield oestradiol. [29, 30] This remarkable achievement was a significant milestone on the long road to synthetic sex hormones. 

Aq. hydroxylamine hydrochloride added with ice-cooling to a soln. of 5 g. 16-hydroxymethylene-Zl -androsten-3y -ol-17-one in alcohol, stored 20 hrs. at room temp., then refluxed 15 min. -> 3.1 g. Zl2 -isoxazolino[4, 5 16,17]-Zl5-androstene-3, 17-diol, 1.2 g. dissolved in benzene, added to a cold coned, soln. of Na-methoxide in methanol, and allowed to stand 1 hr. at room temp. — 0.523 g. 16-cyano-16,17-seco-Zl -androsten-3 -olic-17 acid. K. Bruckner et al., B. 94, 2897 (1961). 

The transformation products introduced during acid hydrolysis are products of dehydration, halogenation, and rearrangement. Dehydration may occur at sites distant from the carbon atom involved in the conjugate as in the formation of A <">-androstene-3a-ol-17-one and -etiocholene-3a-ol-17-one from the corresponding ll 3-hydroxy compounds (83). It may also occur during the course of the hydrolysis of a sulfate ester as in the conversion of androsterone sulfate to A -androstene-17-one (126). 

The abstraction of hydrogen leading to the ketene (Formula 240) is stereospecific giving the 13a-configuration. The same acid (Formula 241) is obtained from 5-androsten-3/8-ol-17-one (Formula 242) and from the C-13 epimer (Formula 243) (91). 

Amino nitroxides, 383 5-Aminotetrazoles, 336, 337 N-Amino-2,4,6-triphenylpyridinium perchlorate, 409 Ammonium acetate, 11 Ammonium cerium(IV) sulfate, 56 Ammonium metavanadate, 418 5a-Androstane-3(3.17 3-diol, 6 5a-Androstane-3d-ol-17-one, 6 A -Androstene-3,17-dione, 167 Angustmycin, 407 2,S -Anhydronucleosides, 88 Anhydrovinblastine, 389 Anion exchange resins, 69 Annelation, 71, 90, 148 Anthraquinone, 29 Anthrasteroids, 167 Antimony(V) chloride, 12 Apomorphine, 236... 

In 1952, Frank B. Colton (1923-2003) at Searle synthesised and later patented norethynodrel, an isomer of norethisterone. An improved synthesis emerged, in which both compounds were obtained, while the aromatisation and Birch reduction could be avoided. [41,42] As starting point serves 5-androsten-3/l-ol-17-one acetate, to which hypochlorous acid is added. Notable is the thermal or photochemical functionalisation of C-19 with lead tetraacetate/iodine, [43] under formation of a cyclic ether. Hydrolysis ofthe ester and oxidation with chromium trioxide leads to a A -enedione, while HCI is eliminated. Reductive opening ofthe ether gives the 19-hydroxy-compound, which can be oxidised with chromium trioxide to the lOjS-carboxylic acid and then decarboxylated in... 

Useful oxidation of alcohols to ketones has been known since the work of Bertrand in 1896. " The application of this reaction to steroid chemistry was first made by Mamoli and his collaborators (S-808, V-1047), who showed that 5-androstene-3/3,17/3-diol could be oxidized to 4-androstene-3,17-dione with bacteria isolated from contaminated yeast. The same crude culture also oxidized 5-pregnen-3/3-ol-20-one to... 

Names synonyms ANDROSTERONE cis ndrosterone 3 4iydrox]r-17-andro ianone androstane>3fl ol-17 methyltesiosterone 9a>Auoro l IA l7/ 4ibydroxy 17c methyl>4-androsten 3 e. ALDOSTERONE electrocortin 18 oxoconicosierone 18 formyM 1 A 2l dthydroxy-4> pregnene>3.20-dione. 

Dana2ol was prepared from 4.32 grams of 17a-ethynyl-2-hydroxymethylene-4-androsten-17(3-ol-3-one, 1.00 gram of hydroxylamine hydrochloride, 1.12 grams of fused sodium acetate and 135 ml of acetic acid. To a 500 ml, 3-necked flask, equipped with a sealed Hershberg-type stirrer, a reflux condenser and a stopper, was added the above androstenone derivative in 300 ml of 95% ethanol. Stirring was commenced and a slurry of fused sodium acetate and hydroxylamine hydrochloride in glacial acetic acid was added. 

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