Androstenes derivatives

Collection of the GC effluent and subsequent MS analysis allowed assignment of a possible molecular formula as Ci9H280. Since boar taint can be eliminated by castration of male pigs, attention was focused on the testosterone and androsterone family of compounds as possible candidates. When the crude volatiles were treated with 2,4-dinitrophenylhydrazine, the boar taint odor was completely removed, implicating a ketone functionality for the lone oxygen atom. Anecdotal information implicated several androstene derivatives, including 47, which was described as having an intense, urine-like odor. 143 An authentic sample of 47 was prepared, and comparison of the GC and MS properties allowed the definitive structural identification of the boar taint compound. 

I7j8-hydroxy-5a-androst-2-ene (A-38), and 2-hydroxymethyl-17a-methyl-17)3-hydroxy-5a-androst-2-ene (A-26), among the 5a-androstene derivatives containing ring A unsaturation. 

In Anlehnimg an Arbeiten auf dem Corticoid-Gebiet wurde in ent-sprechende Androsten-Derivate ein Fluoratom eingefiihrt. Das 9 a-Fluor-11 B-hydroxy-17 a-methyltestosteron = Fluoxymesteron... 

Yields of saturated ketones obtained over Pt or Pd catalysts are improved when a secondary amine is added. The 7-keto-/i -androstene derivative, 1, is reduced to the corresponding 7-ketoandrostane, 2, in 50% yield over 10% Pd-on-carbon. In presence of pyridine, the yield is 90% ... 

Certain androstene derivatives are male sex hormones in higher animals (E 3.1). The most important ones in man are androstenedione and testosterone, which are produced in the testes. In the target tissues, e.g., the prostate gland testosterone is reduced to 5a-androstane-17 -ol-3-one, which seems to be the real metabolic effector. The androstenedione and testosterone that accumulate in certain plant cells, e.g., in the pollen of Pinus sylvestris probably have an ecological function (E 5.5.3). 5a-Androst-16-en-3-one and 5a-androst-16-en-3 x-ol are sex pheromones of the boar (E 4). 5oc-Androst-16-en-3-one is also a constituent of human urine (the urine of males containing three times the concentration of the urine of females) and 5a-androst-16-en-3oc-ol was shown to occur in the sweat of male humans. 

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. 

Sitosterol is an abundant and low-cost raw material for the production of pharmaceutical steroids. 4-Androstene-3,17-dione, the precursor for the synthesis of corticosteroid hormones, can be derived from the side-chain cleavage of/3-sitosterol. Immobilized cells of Mycobacterium sp. NRRL B-3805 on Celite matrix (80-120 mesh) was found to be effective in cleaving the side chain of /3-sitosterol (5gL ) with a molar conversion yield of 70% in 50 h [30],... 

Shoppee, C. W. Steroids and the Walden Inversion. Part II. Derivatives of d5-Cholestene and zl5-Androstene. J. chem. Soc. [London] 1946, 1147. 203- Siegel, S., and C. G. Bergstrom The Effect of a Cyclopropyl Group on a Displacement Reaction at an Adjacent Saturated Carbon Atom. I. The Ethanolysis of Cyclopropylmethyl Benzenesulfonate. J. Amer. chem. Soc. 74, 145 (1952). 

Derivatives of the steroids androstene and pregnene have been transformed directly into A-acyl amino acids by an orthogonal catalysis procedure, utilizing [RhCl(nbd)]2 and Co2(CO)8 (Scheme 11). The rhodium phosphine catalyst (generated in situ in the presence of syn-gas and phosphine) affects hydroformylation of the internal olefin to generate aldehyde. In the presence of Co2(CO)8, A-acyl amino acids are obtained as the major products. An unstable amido alcohol intermediate, formed by reaction of the amide with aldehyde, is proposed to undergo cobalt-catalyzed GO insertion to yield the desired A-acyl amino acid. 

Therefore we used 4-androsten-3,17-dione 1 and 5a-androstan-3,17-dione 2 as model substrates to investigate the chemo- regio- and stereoselectivity of hydrogen transfer from different secondary alcohols, 2-propanol, 2-octanol, cyclohexanol, 1-phenyl-ethanol and diphenylmethanol in the presence of CU/AI2O3. In particular, hydrogenation of 1 allowed to determine the selectivity towards 5p isomers, whereas the percent of axial alcohol was derived from the hydrogenation of 2. These results can be compared with those obtained with the same catalyst in the presence of molecular hydrogen. 

This cyclization method has been applied in the synthesis of the C-ring aromatic analog, 4-androstene-3,17-dione derivative 236. Two cyclizations and the subsequent hydroxylation take place under superacidic conditions846 [Eq. (5.307)]. 

For example the 0-tetrahydropyran.yl derivative of 3g- hydroxy 17-oxo 5-androstene 8 reacted on the bianion and give after metha-nolysis of protective group the 3g, 178— dihydoxy 5-androstene 17a- propanoic acid y-lactone 9 (4). ... 

Whereas a,/ -unsaturated ketones afforded with DIB a-hydroxy-/ -methoxy dimethylacetal derivatives (Section 3.2.2), some steroidal ketones of this kind showed a deviation when treated with o-iodosylbenzoic acid for example, 4-androstene-3,17-dione gave a mixture of two methoxy derivatives and a diene [5]. Several sulphides were oxidized efficiently to sulphoxides by o-iodosylbenzoic acid in acetic acid-sulphuric acid, at room temperature [3]. o-Iodosylbenzoic acid is an excellent reagent for the rapid, catalytic cleavage of reactive esters, especially phosphates, some of which are in stock in big quantities for use as potential nerve gases. This kind of reactivity has drawn considerable attention, and several analogues of the parent acid showed better catalytic activity among them, a series of structurally interesting pyridinium 1,5-zwitterions should be mentioned [6] ... 

Annelation of steroidal dienamines with substituted phenacyl bromides (7 examples) or with benzenediazonium salts (11 examples) has been shown to lead to the corresponding furano- and indolo-steroids.89 Thus the A3,5-dienamine derived from A4-androstene-3,17-dione reacted with p-bromophenacyl bromide to yield the A5-androstano[3,4-h]furan (199) in 26% yield, and reaction of the same A3,5-dienamine with benzenediazonium fluoroborate at -45 °C led to formation of the hydrazone (200) which underwent Fischer-indole cyclization on treatment with phosphorus oxychloride to produce the A4-androstano[6,7-6]indole (201). The A3,5-dienamine derived from 17/3-acetoxyandrost-4-en-3-one has been converted into the benz[4,5,6]-steroid (202 R1 = Me, R2 = H) by reaction with methyl vinyl ketone and into the analogous benzsteroid (202 R1 = H, R2 = Me) on treatment with crotonal-dehyde.90 A route to the condensed pyrroline ring system (203) has been devised... 

In the case of steroidal propargylic alcohols the first rearrangement produced a mixture of allenyl sulfoxides, epimeric at the sulfur atom, which reacted with an added nucleophile to produce substituted allylic sulfoxides. Rearrangement of the sulfoxide resulted in the exclusive formation of a-hydroxy derivatives. This reaction sequence has been applied in a synthesis of hydrocortisone acetate74 (Nu = OCH3) from androstene-3,17-dione and in a transformation of mesantrol75 (Nu = malonate) to a spirolactone. 

The metabolism of 17)3-hydroxy-l-methyl-A -androstene-3-one is markedly different from that of testosterone. In addition to the large amount of unchanged compound, small amounts of l-methyl-A -andro-stene-3,17-dione and la-methyl-androstane-3,17-dione also are excreted in the urine, but the 1-methylated androsterone or etiocholane derivatives are not found [275]. 

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). 

Metabolism studies. GC-MS is a powerful technique for following and identifying the metabolic products from the in vitro incubation of tissue preparations with steroid substrates. Examples of such studies include the 16a-hydroxylation of 18-hydroxydeoxycorticosterone by human adrenal gland [254], the eiromatization of 3jS,15, 16 -trihydroxy-5-androsten-17-one by placental homogenates [255], and the demonstration of 1/3, 12/3, 6a and 6/3 hydroxylase enzyme activities in microsomal preparations of human foetal hepatic tissue [256]. In the latter study, testosterone was used as substrate and in addition to the hydroxylated metabolites isolated, several other testosterone derivatives indicated the presence of 3a, 3/3 and 17/3-hydroxysteroid oxidoreductase in the adrenal gland preparation. 

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. 

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