Testosterone double bonds

In pyridine, as in 2-propanol, the selectivity of reduction favors the A" -3-ketone over the 17- and 20-ketones.Kupfer suggests that resonance interactions between the double bond and the 3-ketone are smaller in pyridine and in 2-propanol than in methanol. However, by slow addition (1 hour) of one equivalent of NaBH4 in pyridine to a solution of androst-4-ene-3,17-dione i n methanol, testosterone has been obtained in good yield (72 %). Similarly,... 

Testosterone is metaboHzed by two pathways. One involves oxidation at the 17 position, and the other involves reduction of the A ring double bond and the 3-ketone. Metabohsm by the first pathway occurs in many tissues, including liver, and produces 17-ketosteroids that... 

Formal isomerization of the double bond of testosterone to the 1-position and methylation at the 2-position provides yet another anabolic/androgenic agent. Mannich condensation of the fully saturated androstane derivative 93 with formaldehyde and di-methylamine gives aminoketone 94. A/B-trans steroids normally enolize preferentially toward the 2-position, explaining the regiospecificity of this reaction. Catalytic reduction at elevated temperature affords the 2a-methyl isomer 95. It is not at all unlikely that the reaction proceeds via the 2-methylene intermediate. The observed stereochemistry is no doubt attributable to the fact that the product represents the more stable equatorial isomer. The initial product would be expected to be the p-isomer but this would experience a severe 1,3-diaxial non-bonded interaction and epimerize via the enol. Bromination of the ketone proceeds largely at the tertiary carbon adjacent to the carbonyl (96). Dehydrohalogenation... 

A somewhat related sequence leads to trilostane (111), a compound that inhibits the adrenal gland more specifically the agent blocks some of the metabolic responses elicited by the adrenal hormone ACTH in experimental animals. Reaction of the hydroxy-methylene derivative 108, obtained from testosterone, with hydroxylamine gives the corresponding isoxazole (109). Oxidation of the C-4,5 double bond by means... 

The major pathway for the degradation of testosterone in humans occurs in the liver, with the reduction of the double bond and ketone in the A ring, as is seen in other steroids with a A4-ketone configuration in the A ring. This leads to the production of inactive substances such as androsterone and etiocholanolone that are then conjugated and excreted in the urine. 

Additional activation of the 3-OH group by an allylic double bond increases the selectivity and leads to 50% testosterone (27). Cholic acid is oxidized exclusively at the 3a-position without any attack at the 7a- and 12a-hydroxy groups. Comparable selectivities have been reported for oxidations by silver carbonate on celite and by molecular oxygen with a platinum catalyst The yield of 23 is however lowered by a competing reaction to the lactone 24 this is formed by oxidative cleavage of the C3—C4 bond, followed by lactonization during work-up. 

Cholesterol is the most common steroid of mammalian membranes. It is formed biologically from lanosterol, as shown. Ergosterol is the most common steroid of fungal membranes. It differs from cholesterol by the presence of two additional double bonds that affect its three dimensional structure. Also shown are three so-called steroid hormones, andros-terone, estradiol, and testosterone. Note the presence of an aromatic A-ring in estradiol. 

If as above we simply represent alicyclic rings sharing two Gs by a vertical line, then we can represent the basic tetracyclic structure of lanosterol as G61G61 G6 C5 (noting that there are two double bonds and various alkyl substituents and also a 3-hydroxyl on the first of the alicyclic rings). Many subsequent reactions yield cholesterol, a major triterpene membrane component that modifies the fluidity of animal cell membranes and is a precursor for synthesis of animal bile acids (fat solubilizing amphipathic detergents) plant triterpenes and steroid hormones such as the corticosteroids cortisol and cortisone, the mineralocorticoid aldosterone and the sex hormones testosterone and 17-(3-oestradiol. The structure and bioactivity of the plant terpenes is sketched below. 

The natural androgen testosterone and a large number of other androgens and anabolic agents possess the 4,5-double bond, while the majority of metabolic products lack this unsaturation. The hypothesis was put forward that the reduction of the 4,5-double bond in the liver may represent the rate-limiting step in the inactivation of these hormones [168,221]. Upon hydrogenation of the double bond, the 5-carbon becomes asymmetric and therefore two possible isomers could result, the 5a-isomer (trans... 

The most important function of the 4,5-double bond seems to be the protection of the 3-carbonyl function against metabolic inactivation. It is known that 5a-dihydrotestosterone is a more powerful androgen than testosterone, especially when measured by the ventral prostate index. 

However, the 3-carbonyl function is metabolized much faster in 5a-dihydrotestosterone than in testosterone where the 4,5-double bond has a rate-limiting effect, i.e., the metabolic inactivation of 3-carbonyl group is much faster than the reduction of 4,5-double bond [168,221]. 

Comparison of 17a-methyltestosterone (S-2), 17a-methyl-5a-dihydro-testosterone (D-2), and 17o -methyl-d -testosterone (S-107) revealed that the presence of the double bond in the 4,5-position enhanced the anabolic activity and did not alter the androgenic activity, according to Beyler et al. [124]. Additional unsaturation lowered both anabolic and androgenic activities, but decreased the anabolic activity to a lesser degree. 

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