Testosterone hydrogenation

A solution of testosterone (54 10 g) in 300 ml methanol is cooled to 0° and treated successively with 60 ml of cold 30 % hydrogen peroxide and 20 ml of cold aqueous 10% sodium hydroxide. The reaction mixture is stored for 48 hr at 0° and then poured into ice water. The resultant oil is extracted with methylene dichloride (or ether) and the extract is dried (MgS04). Removal of the solvent affords the crude product, a mixture of 4a,5a- and 4, 5 -isomers, which is purified by chromatography. A sample of pure 17j5-hydroxy-4/3,5 -oxidoandrostan-3-one, mp 157-158°, crystallizes after trituration of the crude product with ether. 

Photoketone (118) has served as the key intermediate in a relatively simple transformation of 3-keto-10/ -steroids to 3-keto-lOa-isomers without the assistance of other functional groups suitably situated next to the ring junction—a task that appears difficult to attempt by other methods. Optimal yields of (118) are achieved by catalytic hydrogenation of the unsaturated ketone (175), the photoisomer of 1-dehydrotestosterone acetate (see section III-C). In this way, a 6-step conversion of 1-dehydrotestosterone acetate (174) to IOa-testosterone acetate (127 acetate) is achieved in good yield. ° ... 

K. Eto and H. Kimura, The production of hydrogen sulfide is regulated by testosterone and S ndcnosyl L-methionine in mouse brain. J. Neurochem. 83, 80-86 (2002). 

A second example can be found in the metabolism of the male sex steroid hormone testosterone. In addition to 7a -hydroxy- and 6a-hydroxytestosterone, CYP2A1 was also found to form A6-testosterone (136) (Fig. 4.69). Using selectively deuterated analogs (136), A6-testosterone was established as being formed in competition with 6o -hydroxytestosterone after initial hydrogen atom abstraction from C6 to form the common radical intermediate. Little, if any, A6-testosterone was found to be formed in competition with la-hydroxytestosterone after initial hydrogen abstraction from Cl. 

TABLE 3-1 Percent Cis Ring-fused Product Obtained on Hydrogenation of Octal-1 (9)-en-2-one (9), Testosterone and Cholestenone... 

The retention of tritium at C(2) in the conversion of testosterone to estradiol is interpreted as the result of triitium IE associated with enolization of 4-dien-3-one intermediate. The enolization follows after the deformylation and 1/i-hydrogen abstraction steps and is... 

Steroid hormones bear a remarkable structural similarity to one another (see Fig. 29-1). The precursor for steroid biosynthesis is cholesterol. Consequently, all of the steroid hormones share the same basic chemical configuration as their parent compound. This fact has several important physiologic and pharmacologic implications. First, even relatively minor changes in the side chains of the parent compound create steroids with dramatically different physiologic effects. For instance, the addition of only one hydrogen atom in the sex steroid pathway changes testosterone (the primary male hormone) to estradiol... 

Testosterone contains 19 carbon atoms in a four-ring structure, with each numbered from one to 19. Modifications in the carbon atoms creates the hundreds of synthetic AASs that exist today. For example, many common synthetic forms of testosterone have alterations on their seventeenth carbon. AASs created in pill form have an added alkyl group, which is a chain of carbon and hydrogen atoms. These 17-alkylated AAS compounds are more toxic to the liver and more likely to cause cholesterol abnormalities. Common 17-aldylated AASs include Dianabol, Android, and Winstrol. When the addition to the seventeenth carbon is an ester, which is an acidic chain of carbon and hydrogen, the synthetic form is an injectable form that is less toxic on the liver and cholesterol levels. Depo-Testosterone is an example of the injectable testosterone ester. AAS abusers also use veterinary products, such as Finajet and Equipoise, that have been devised for animal usage. 

P-Cyclopentylpropionic acid Testosterone 3-enol-ethyl ether Acetic anhydride Hydrogen chloride... 

Fig. 4.1 Correlation of permeability and total hydrogen-bonding capacity for a series of structural heterogeneous compounds corticosterone (Co), testosterone (Te), propranolol (Pr), alprenolol (Al), warfarin (Wa), metoprolol (Me), felodipine (Fe), hydrocortisone (Hy),...

Solvent Effect on 5fl-Product Formation in the Hydrogenation of Cholestenone and Testosterone... 

In aprotic solvents, an increase in solvent polarity resulted in an increase in the amount of ds-0-decalone formed. Similar results were also obtained in the hydrogenation of cholestenone and testosterone (see Table I). If, as suggested by McQuillin et al. (3), a more polar aprotic solvent will facilitate complexation of the carbonyl oxygen of an a,j3-unsaturated ketonic system in the same way that it increases its polarization (25), it can be assumed that what is occurring in these polar solvents is a 1,4-addition of hydrogen to the conjugated system. 

The differences noted in Table I in the hydrogenation of cholestenone and testosterone are probably due to differences in solvent acidity used in each case. This is difficult to check since the acid concentrations used were not always reported. It is further possible that with substrates such as A4-3-ketosteroids the acid concentrations corresponding to the two product distribution breakpoints shown in Fig. 6 are different from those found for octalone hydrogenation. Thus, the change in acidity between alcoholic HC1 and alcoholic HBr could correspond to a change analogous to that found between the two breakpoints in Fig. 6. 

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