Androsten-3,17-dione

Bacterial removal of sterol side chains is carried out by a stepwise P-oxidation, whereas the degradation of the perhydrocyclopentanophenanthrene nucleus is prevented by metaboHc inhibitors (54), chemical modification of the nucleus (55), or the use of bacterial mutants (11,56). P-Sitosterol [83-46-5] (10), a plant sterol, has been used as a raw material for the preparation of 4-androstene-3,17-dione [63-05-8] (13) and related compounds using selected mutants of the P-sitosterol-degrading bacteria (57) (Fig. 2). 

DHEA(23) 4-Androstene-3,17-dione —> Estrone (26) Estrogens Cortisone (31)... 

Selective conversion of l,4-androstadiene-3,l7-dione to 4-androsten-3,17-dione was achieved with (Ph Pi RuClj (SI), prepared by refluxing ruthenium... 

Weakly fluorescent zones were visible under long-wavelength UV light (X = 365 i (Fig. 1). Cortisone (h/ f 0-5), dienestrol (h/ f 10-15), 4-androstene-3,17-dione (It 50-55) and 4-cholesten-3-one (h/ f 60-65) had an ochre fluorescence. Diethylsti estrol (h/ f 10-15), 17a-ethinyl-l,3,5-estratriene-3,17B-diol (h/ f 25-30) and estro (h/ f 35-40) had a blue emission. 

Fig. 1 Fluorescence scan of a chromatogram track with 1 ng cortisone (1), 100 ng dienestrol (2X 300 ng 17a-ethinyl-l,3,5-estratriene-3,17B-diol (3), 100 ng estrone (4) and 1 ug each of 4-androstene-3,17-dione (5) and 4-cholesten-3-one (6) A. before immersion in Triton X-100, B. after immersion followed by brief drying, C after heating to 120 °C for 10 minutes and D. for a further 20 minutes to increase the fluorescence.

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],... 

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... 

In the particular case of 1,4-androstadien-3,17-dione regioselectivity promoted by copper was better than that exhibited by any catalytic system previously reported, giving up to 72% of 4-androsten-3,17-dione (93% regioselectivity). 

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)]. 

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

Fig. 10.15. Gradient elution CEC separation of steroid hormones. Conditions capillary, 9.6 (17.6) cm x 50 pm i.d. packed with 6 pm Zorbax ODS mobile phase, A, acetonitrile-10 raM borate, pH 8 (65 35 v/v) B, acetonitrile-10 mM borate, pH 8 (85 15 v/v), 0-100% B in 5 min, 100% B for 3 min at 0.1 ml/min 14 kV 25°C detection, UV at 205 nm injection, 1 kV/0.5 s. Peak identification 1, formamide 2, corticosterone 3, testosterone 4, androsten-3,17-dione 5, androstan-3,17-dione 6, pregnan-3,20-dione. Reproduced with permission from Huber et al. [68]. Copyright 1997 American Chemical Society.

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] ... 

Androstene-3,17-dione can be transformed selectively into the 17-ethylenehemithio acetal in the presence of the a,P-unsaturated carbonyl system. The parent andros-tenedione can be regenerated by treatment of the hemithio acetal with Raney Ni (eq. 13.82) by the reaction of eq. 13.79.160... 

---