Androst-5-ene-3,17-dione

Ketonic carbonyl groups are commonly encountered in steroids and their reduction is facile, even in the absence of an alcohol. The lithium-ammonia reduction of androsta-l,4-diene-3,17-dione affords androst-4-ene-3,17-dione in 20% yield but concurrent reduction of the C-17 ketone results in formation of testosterone in 40% yield, even though the reduction is performed rapidly at —40 to —60° and excess lithium is destroyed with solid ammonium chloride. Similar reduction of the C-17 carbonyl group has been observed in other compounds. In the presence of an alcohol, a ketone is complete-... 

A variety of conjugated dienones are reduced by lithium-ammonia, presumably via dienyl carbanions analogous to the allyl carbanions encountered in enone reductions. Cross-conjugated l,4-dien-3-ones afford 4-en-3-ones as the major reduction products, indicating that the cyclohexadienyl carbanion (55) protonates largely at C-1. Some protonation at C-5 does occur as shown by examination of the NMR spectrum of the crude reduction product derived from the 17-ethylene ketal of androsta-l,4-diene-3,17-dione. The 17-ethylene ketal of androst-4-ene-3,17-dione is formed in 75%... 

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,... 

Androst-4-ene-3,17-dione. Testosterone (0.58 g, 2 mmoles) is dissolved in a solution prepared from 3 ml of benzene, 3 ml of dimethyl sulfoxide, 0.16 ml (2 mmoles) of pyridine and 0.08 ml (1 mmole) of trifluoroacetic acid. After addition of 1.24 g (6 mmoles) of dicyclohexylcarbodiimide, the sealed reaction flask is kept overnight at room temperature. Ether (50 ml) is added followed by a solution of 0.54 g (6 mmoles) of oxalic acid in 5 ml of methanol. After gas evolution has ceased ( 30 min) 50 ml of water is added and the insoluble dicyclohexylurea is removed by filtration. The organic phase is then extracted twice with 5 % sodium bicarbonate and once with water, dried over sodium sulfate and evaporated to a crystalline residue (0.80 g) which still contains a little dicyclohexylurea. Direct crystallization from 5 ml of ethanol gives androst-4-ene-3,17-dione (0.53 g, 92%) in two crops, mp 169-170°. 

The reaction of androst-4-ene-3,17-dione with DDQ in refluxing benzene or dioxane leads to the A -3-ketone as the major product, although small amounts of A -3-ketone and A -3-ketone are also produced. The latter arises from the A -3-ketone, since the A -3-ketone is not dehydrogenated further under the usual reaction conditions. A -3-Ketone production is more favored in benzene than it is in dioxane substituents at C-6 can also influence this selectivity. A recent thorough investigation of the mechanism of dehydrogenation of 3-ketones under neutral and acidic condi-... 

Androst-4-ene-3,17-dione (83) is converted into the enol ether (84) by reaction with triethyl orthoformate. Treatment of the enol ether (84) with DDQ in aqueous acetone gives the title dienone (85). This method is particularly suitable for A" -3-ketones substituted at the 6-position. 

The effect of the catalyst-steroid ratio has been studied for the p-toluene-sulphonic acid-catalyzed ketalization of androst-4-ene-3,17-dione. Selective formation of the 3-monoketal is observed with the use of an equimolar amount of ethylene glycol and a low ratio of catalyst to steroid. ... 

Androst-4-ene-3,l7-dione 3-Ethylene Thioketal A solution of androst-4-ene-3,17-dione (1.42 g, 5 mmoles) in acetic acid (20 ml) is treated with ethanedithiol (0.47 g, 5 mmoles) and a solution of 0.45 of p-toluenesulfonic acid monohydrate in acetic acid (5 ml). After 1 hr at room temperature, the pale yellow solution is poured into water and the resulting suspension is extracted with chloroform. The chloroform solution is washed with water, 5 % sodium hydroxide solution and water, dried (Na2S04) and evaporated. Chromatography of the resulting oil (1.93 g) over silica gel yields androst-4-ene-3,17-dione bisethylene thioketal, mp 173-175° [0.16 g, eluted with petroleum ether-benzene (1 2)] and androst-4-ene-3,17-dione 3-ethylene thioketal, mp 173-176° [1.38 g (76%), eluted with benzene-ethyl acetate (19 1)]. 

The use of acetone cyanohydrin (in an exchange reaction) instead of alcoholic hydrogen cyanide affords even higher yields of 17-cyanohydrins and the former reagent has the added advantage of reacting quantitatively and essentially selectively with the 17-ketone of androst-4-ene-3,17-dione. Sodium hydroxide promotes the exchange reaction in some cases. 

Cyano -17 - hydroxy androst- 4- en - 3 - one Androst - 4- ene -3,17- dione (20 g) is dissolved by gentle warming in 30 ml of freshly prepared acetone cyanohydrin.Crystallization begins in a few minutes and is complete... 

Androst-4-ene-3,17-dione 17a-Hydroxyprogesterone (1 g) is dissolved in 10 ml of pyridine and treated dropwise at —20° with a solution of nitrosyl chloride in pyridine until a permanent blue color develops. The reaction is quenched with 500 ml of ice water, and the resulting nitrite is filtered and... 

Penicillium lilacimm transformed testosterone successively to androst-4-ene-3,17-dione and testololactone (Prairie and Talalay 1963) once again the oxygen atom is introduced into ring D at the quaternary position between C13 and C17. 

This enzyme [EC 1.1.1.51] catalyzes the reaction of testosterone with NAD(P)+ to produce androst-4-ene-3,17-dione and NAD(P)H. The enzyme can also use other 3/3- or 17/8-hydroxysteroids as substrates. 

In the rat, development to adult levels of activity takes about 30 days after which levels decline toward old age. In humans, however, hydroxylase activity increases up to the age of 6 years, reaching levels greater than those in the adult, which only decrease after sexual maturation. Thus the elimination of antipyrine and theophylline was found to be greater in children than in adults. It should be noted, however, that proportions of isoenzymes may be very different in neonates from the adult animal, and the development of the isoenzymes may be different. Thus, in the rat there seem to be four types of development for phase 1 metabolizing enzymes linear increase from birth to adulthood, type A (aniline 4-hydroxylation) low levels until weaning, then an increase to adult levels, type B (N-demethylation) rapid development after birth followed by rapid decline to low levels in adulthood, type C (hydroxylation of 4-methylcoumarin) and rapid increase after birth to a maximum and then decline to adult levels, type D. Patterns of development may be different between sexes as well as between species. For example, in the rat, steroid 16-a-hydroxylase activity toward androst-4-ene-3,17-dione develops in type B fashion in both males and females, but in females, activity starts to disappear at 30 days of age and is undetectable by 40 days. It seems that the monooxygenase system develops largely as a unit, with the rate dependent on species and sex of the animal and the particular substrate. 

Androst-l-ene-3,17-dione ketal, 32 Androst-4-ene-3,17-dione 17-ethylene ketal, 31... 

---