A -Androstene-3,17-dione

The 10l -acetoxy group can be red actively removed with zinc and acetic acid or chromous chloride to give I9-norsteroids in high yield. Thermal elimination (boiling tetralin) of acetic acid from the crude 10)5-acetoxy-A -3-ketone or treatment with methanolic alkali leads to aromatization of ring A. Estrone alkyl ethers are formed from 10)5-acetoxy-19-nor-A -androstene-3,17-dione by treatment with alcohols and perchloric acid. Similar aromatizations are observed with 5,10-oxido, 5,10-dihydroxy, 5,10-halohydrins or 5,10-dihalo-3-ketones. ... 

In an example of the use of this activation method testosterone, with a IT -hydroxy group, was oxidized to A -androstene-3,17-dione very rapidly in high yield, in contrast to the use DMSO-acetic anhydride. During a reaction, when other oxidizing agents were found to be ineffective, sulfur trioxide/dimethyl sulfoxide led to smooth oxidation of the df-diol (16 equation 8) to an o-quinone in 49% yield and the ci.r-diol (17) to (18 equation 9) in 98% yield. - The use of dimethyl sulfoxide-acetic anhydride for this oxidation gave large amounts of the diacetate as the by-product. 

A -Androsten-3,17-dione (S-22), la-cyano-A -androsten-3,17-dione (S-37), ljS-acetylthio-A -androstene-3,17-dione (S-38), 7a-methyl-A -androstene-3,17-dione (S-23), A -androstene-3,l 1,17-trione (S-43), 11/3-hydroxy-A -androstene-3,17-dione (S-44), 3a -hydroxyandrostane-17-one (D-27), 3/3-hydroxyandrostane-I7-one (D-161), and androstane-3,17-dione (D-30) compared to the corresponding 17/3-hydroxy derivatives exhibit much smaller androgenic and anabolic activities with unfavorable anabolic-androgenic ratios (with the exception of S-23, which has a favorable ratio). 

A -Androstene-3,17-dione gives a 24% yield of 15a-hydroxy-A -an drostene-3,17-dione on treatment with Fusarium Uni at 25-27 °C [1066] and a mixture of the same compound (yield 33%) together with 6p-hy-droxy-A -androstene-3,17 dione (yield 20%) on incubation with Gibberelia saubinetii (in ref. 1066, saubinetti) [1066, 1067] (equation 406). 

Heyl and Herr developed an efficient method for the conversion of A -androstene-3,17-dione into testosterone involving in the first step selective enamine formation at C3. The diketone was refluxed with 4 equivalents of pyrrolidine and a trace of p-toluenesulfonic acid under a water separator, and the reaction was stopped when 1 mole of water had been collected. With the C3 carbonyl function protected," the keto group at C17 could be reduced smoothly. Hydrolysis of the enamine group with a weakly acidic buffer afforded testosterone. 

The reagent reacts with 19-hydroxy-A -androstene-3,17-dione (1) in refluxing acetonitrile to give the 5,19-cyclosteroids (2) and (3). ... 

A -5-Androstadiene-3,17-dione, 461, 462 5 -Androstane-17/S-ol, 377 5a-Androstane-16-one, 243 5< -Androstane-17-one, 243 5a-Androstane-3-one-17fl-ol, 377 Androstanol-3j8, 363 Androstanone-3, 363 A -Androstene-3, 17-dione, 165 A5-Androstene-3/3-ol, 73 A4-Androstene-3,l 1,17-trione, 354 1 Androsterone, 286... 

Fig. 3. Various types of reaction catalyzed by GST. Besides the formation of thioethers, GST catalyze thiolysis, denitrozation, isomerization, and peroxidase-type reactions (see text). As examples of such reactions, the metabolism of p-nitrophenyl acetate, nitroglycerine, A -androstene-3,17-dione, and cumene hydroperoxide are shown in a, b, c, and d, respectively.

Steroid double bond isomerase (1 x 10 with A -androstene -3,17- dione)... 

For oxidation of hydroxy ketones, /-butoxymagnesium bromide, which does not add to ketones, is used as the Grignard reagent. Under these conditions testosterone (2) is oxidized to A -androstene-3,17-dione (3),in 96% yield. 

The yields of derivatives are usually >95%. Moreover this method is useful for selective monothioketalization. Thus A -androstene-3,17-dione can be converted into the 3-dimethyl thioketal in 92%, yield. ... 

Ammonium thiocyanate, 521 A -Androstene-3,17-dione, 20, 352 o -Angelicalactone, 315 Angeloyl chloride, 365 Anilides, 230... 

GSTA3-3—A -androstene-3,17-dione, A -pregnene-3,20-dione, DBPDE. 

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... 

A ( )-3-ketosteroids into the corresponding A -3-ketosteroids. Typical examples of the reaction are the conversion of A -androstene-3,17-dione and A -pregnene-3,20-dione to the respective A -3-ketosteroids (Scheme 1, A and B). 

Considerable information is available on the molecular properties of this enzyme, on the catalytic mechanism, and on the stereochemistry of the enzymic reaction. The isomerase is composed of identical associating subunits. The primary structure is known and comprises 125 residues (MW 13,394) including all the common amino acids except cysteine and tryptophan. The enzyme, which exhibits exceptionally high catalytic activity, has a molecular activity at saturating concentrations of A -androstene-3,17-dione of 4.38 X 10 min per monomer at pH 7.0 and 25°. Mechanistic studies have disclosed that the isomerase catalyzes the reaction of A < -3-ketostcroids by a direct, stercospccific, and intramolecular transfer of the 4 8-proton to the 6)8 position. There is considerable evidence for the involvement of an enolic intermediate in the... 

Aminotransferases, 31, 163, 164, see also specific enzymes Ampicillin, 536 A -Androstene-3,17-dione, 461 Angiotensin, 236 Anhyride analogs, 302-307 2,6-Anhydro-l-diazo-l-deoxy-D-glycero-i-OTonno-heptitol, 36... 

Testosterone itself has been isolated in very small amounts from urine, and then only after administration of large doses of the hormone " — an indication that it is rapidly and completely metabolized in the normal male. The hormone disappears rapidly from the blood after intravenous injection and the metabolites appear promptly in the urine. As yet, testosterone has not been detected in the peripheral circulation although A -androstene-3,17-dione (LV) and testosterone are present in the spermatic venous blood of the dog. The transformation of the hormone by tissues, especially the liver, must be quite rapid and the kidney threshold for the metabolites must be extremely low. 

The first step in the catabolism of testosterone according to Fig. 10 should be the oxidation of the 17/8-hydroxyl group to the ketone to form A -androstene-3,17-dione. Although this substance has been found in the urine of a man with adrenal hyperplasia, normally the turnover of this compound must be very rapid, since it is not present in normal urine and is not found even after the administration of large amounts of testosterone. However, the administration of isotopic, as well as nonisotopic, A -androstene-3,17-dione gave rise to the same metabolites (androsterone, XLVIII, and etiocholanolone, XLIX) as testosterone therefore, A -androstene-3,17-dione could be an intermediate in the biochemical transformation of the testicular hormone. 

A separation in the metabolic route occurs on the reduction of the double bond of A -androstene-3,17-dione (LV), affording two saturated diketones isomeric at Cs. These are rings A/B trans, androstane-3,17-dione (LX), and rings A/B cis, etiocholane-3,17-dione (LXI). Both of these diketones have been isolated from urine. " That these two diketones are true metabolites of testosterone has been shown by the isolation of the tagged substances after injection of deuterium-labeled hormone. Once the metabolic course has diverged upon the reduction of the a, unsaturated ketone to the isomeric diketones, there is no crossing over from one branch of the pathway to the other. Thus, after the administration of either deuterium-labeled or nonisotopic androstane-3,17-dione (LX), only... 

The chemical transformations of testosterone (L) by the liver and the enzyme systems involved have been studied extensively. In rabbit liver slices, the 17 8-hydroxyl group is oxidized to the 17-ketone to give androstene-3,17-dione (LV).i That this transformation takes place is further evidence for the first step in the metabolic scheme outlined in Fig. 10. From the same incubation 17a-hydroxy-A -androstene-3-one (LXX, cfs -testosterone), as well as testosterone, was obtained. Furthermore, incubation of 17a-hydroxy-A -androstene-3-one (LXX) afforded A -androstene-3,17-dione (LV),i and all three products were isolated after incubation of A -androstene-3,17-dione with liver. These results demonstrate that the 17-ketone can be reduced to either a 17a- or 17j8-hydroxyl group and both can be oxidized back to the ketone. Therefore,... 

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