19-Hydroxy-4-androstene-3,17-dione

On angular methylation with protection of the 3o -hydroxy group in the form of the tetrahydropyranyl ether, the furfurylidene derivative (180) formed the trans-C/D and the cis-C/D methyl derivatives (177) and (181), respectively, in a ratio of 1 3.8. Transacetylation, ozonolysis, and esterification of the trans-methyl derivative (177) led to the diester (178), the Dieckmann reaction of which followed by acid hydrolysis gave the hydroxy ketone (179). Oxidation of the 30 -hydroxy group of the latter and the introduction of a A -bond by bromination and dehydrobromination led to the yeast Saccharomyces cerevisiae by a known method [927], a mixture of the c -enantiomer of testosterone (182) and the Z-enantiomer of androstene-dione (183), which were separated chromatographically, was obtained with yields of 70 and 73%, respectively. The over-all yield of Z-testosterone (182) in this synthesis amounted to 2.9% on the (162) (twelve stages) and 1.1% on the unsaturated ketone (140) (16 stages) [921]. 

The second way is from 4-androsten-3,17-dione (21.5.6), which undergoes ethynylation by propargyl alcohol in the presence of potassium tert-butylate, forming 17 8-hydroxy-17a-(3-hydroxypropinyl)-4-androsten-3-one (21.5.9), the triple bond of which is completely reduced by hydrogen using as a catalyst a complex of triphenylphospine and... 

Androsterone 11 p-Hydroxyandrosterone 5-(3-Androstan-17-one 19-Hydroxy-4-androstene-3,17-dione... 

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] ... 

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. 

This sequence was developed for conversion of 9a-hydroxy-4-androstene-3,17-dione, a biodegradation product of the common plant sterol -sitosteTol, to corticosteroids. The transposition of the 9a -hydroxy group to an 11 /3-hydroxy group can be accomplished readily by dehydration to the 9(ll)-ene, addition of HOBr, and reduction of the 9tr-bromine with chromium(II) chloride. 

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). 

C19H2603 4-hydroxy-4-androstene-3,17-dione 566-48-3 25.00 1.0392 2 31722 C19H3803 hexadecyl 2-hydroxypropanoate 35274-05-6 25.00 0.9114 2... 

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). 

A reagent suitable for oxidations of steroidal hydroxy ketones to diketones is dimethyl sulfoxide in the presence of various activators. It converts testosterone into 4-androstene-3,17-dione in 95-100% yields (equation 445) [1016, 1018],... 

NMR spectra of various carbonyl-containing steroids were investigated. - Here, inteimolecular exchange was slow even at 0 °C. In the presence of hydroxy or ether functionality little or no complexation at the carbonyl sites was observed. For BF3/androstene-3,17-dione (Figure 11a) complexation occurred solely on the enone carbonyl of the A-ring, in contrast to S3-androstane-3,17-dione (Figure 1 lb), where the carbonyls of the a- and the o-ring were complexed in a 64 36 ratio. ... 

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

The inactivation of AR by the 10/8-hydroperoxy-4-estrene-3,17-dione (92), a steric mimic of the intermediate 19-hydroxy-4-androstene-3,17-dione (19),... 

Hosoda, H. and J. Fishman (1974). Unusually facile aromatization of 2b-hydroxy-19-oxo-4-androstene-3,17-dione to estrone. Implications in estrogen biosynthesis. J. Am. Chem. Soc. 96, 7325-7329. 

Covey, D.F. and W.F. Hood (1982). Aromatase enzyme catalysis is involved in the potent inhibition of estrogen biosynthesis caused by 4-acetoxy- and 4-hydroxy-4-androstene-3,17-dione. Mol. Pharmacol. 21, 173-180. 

C.-H. Tsai-Morris, P.A. Marcotte, and C.H. Robinson (1981). Inactivation of aromatase in vitro by 4-hydroxy-4-androstene-3,17-dione and 4-acetoxy-4-androstene-3,17-dione and sustained effects in vivo. Steroids 38, 693-702. 

Names synonyms ANDROSTERONE cis>androsterone 3ai-hydroxy-17-androstanone androstane-3a>ol> 7 one. FtUOXYMESTERONE 9a fluoro 11 hydroxy 17 methyltesiostcrone 9s>fluoro l I/U7/ >dihydroxy l7a methyi 4-androsten 3 one. ALDOSTERONE electrocorttn 18 oxocorticosterone 18 formyM l/ .2l dthydroxy-4> pregnene>3.20 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. 

---