4-androstene-3,17-diol

Merck reported that certain 19-substituted androstene diol derivatives exhibited a remarkable degree of ERP selectivity [103]. However, in many cases the compounds... 

On a dark background cholesterol (Eluent A, h/ f 20-25) emitted blue, coprostanol (Eluent A, h/ f 25-30) blue, 4-cholesten-3-one (Eluent A, h/ f 40-45) blue, 5a-cholestan-3-one (Eluent A, h/ f 60) blue, coprostanone (Eluent A, h/ f 70) blue, estriol 3-sulfate (Eluent B, h/ f 5-10) yellow, 11-ketoetiocholanolone (Eluent B, h/ f 15-20) blue, estrone (Eluent B, h/ f 20-25) ochre, 11-desoxycorticosterone (Eluent B, h/ f 30-35) yellow, 17a-ethinyl-5-androstene-3p,17p-diol (Eluent B, hRj 45-50) ochre, 4-cholesten-3-one (Eluent B, h/ f 55-60) faint blue and coprostanone (Eluent B, h/ f 65-70) violet fluorescences. 

Fig. 2 Fluorescence scan of a chromatogram track with 100 ng each of estriol-3-sulfate (1), 11-ketoetiocholanone (2), estrone (3) 11-desoxycorticosterone (4) and 17a-ethinyl-5-androsten-3P,17P-diol (5), together with 1 pg each of 4-cholesten-3-one (6) and coprostanone (7) per chromatogram zone.

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.

WeEl-Engerer S, David JP, Sazdovitch V, Liere P, Schumacher M, et al. 2003. In vitro metabolism of dehydroepiandrosterone (DHEA) to 7alpha-hydroxy-DHEA and Delta5-androstene-3beta,17beta-diol in specific regions of the aging brain from Alzheimer s and non-de-mented patients. Brain Res 969 117-125. 

The 13,17-seco-acid lactone (258), obtained from a Baeyer-Villiger oxidation of 5a-androstan-17-one has been reduced to yield 13,17-seco-5a-androstan-13a,17-diol, whose diacetate on pyrolysis furnished the endocyclic seco-olefin (259 R = OAc) as the major reaction product. A minor product is the corresponding A12 13-olefin.115 Hydrolysis of the acetate (259 R = OAc) to its alcohol (259 R = OH) and formation of the tosylate and the iodide (259 R = I), followed by reaction with lithium dimethylcuprate, afforded a route to A1314-13,17-seco-5a-D-homoandrostene (259 R = Me). The [17a,17a,17a-[2H3]androstene (259 R = CD3) was prepared by treating the iodide (259 R = I) with lithium perdeuteriodimethyl-cuprate. 

The early functional models for this oxidation chemistry were rather simple Udenfriend used iron(II), EDTA, ascorbic acid (as the reducing agent) and O2 to hydroxylate arenes, while Hamilton showed that the same system hydroxylates unactivated C—H bonds (e.g. androsten-3-ol-17-one is converted to androsten-3,7-diol-17-one). Mimoun developed the use of an iron(II)/PhNHNHPh/ H1CO2H/O2 system which is also active for alkane hydroxylation. Curiously, other metals [copperfll), manganese(II), vanadium(II), cobalt(II)] are also active. In the hydroxylation of arenes, an arene oxide is believed to be the intermediate in P-450 dependent systems, because a 1,2-shift of a proton in the arene, the NIH shift is often observed. Neither the Udenfriend nor Mimoun models show such a shift, however. 

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. 

Disposition in the Body. Testosterone is the androgenic hormone formed in the testes. In man, it is metabolised to 5a-androstane-3a,17)5-diol, androsterone, etiocholanolone, and 5a-androstene-3,17-dione. In the horse, the major metabolites are 5a-androstane-3)5,17a-diol, which is excreted in the urine as the glucuronide conjugate, and the 17)5-epimer which is excreted in the urine as the sulphate conjugate. 

Acetoxy-5-androsten-17-one Me (OBu")3 CH2CI2 Overnight -20 to+20 17a-Methyl-5-androstene-3p, 17p-diol 80... 

A5 - A 7-Steroid. Dauben and Fullerton chose the following route for conversion of A5-androstene-3/ ,l 7/5-diol diacetate (1) into A5 7-androstadiene-3/ , 17/3-diol diacetate (4). The starting material was converted into the 7-ketone (2) by oxidation with chromium trioxide-pyridine complex in methylene chloride (2,74-75). The ketone... 

N-Acetylamino-L-tryptophane, 530 17a-Acetyl-A -androstene-3/5,l 7 S-diol, 660 9-Acetylanthracene, 27, 131 a-Acetyl-T-butyrolactone, 676 Acetyl chloride, 11, 263-264, 275, 336 2-, 4-, and 5-Acetylchrysene, 676-677 S-Acetylcoenzyme A, 1157... 

Shackleton, C. H. L., Livingstone, J. R. B., and Mitchell, F. L., The conjugated 17-hydroxy epimers of A -androstene-3/3-17-diol in infant and adult urine and umbilioal cord plasma. Steroids 11, 299-311 (1968). 

Hydroxylation. Maume and Horning2 report that trimethylsilyl (TMSi) enol ethers of ketosteroids when irradiated with UV light (dibenzoyl peroxide can also be used) are converted into the trimethylsilyl derivative of an a-hydroxy ketone. Thus the TMSi enol ether of A5- mdrostene-3/3-ol-17-one (1) gives (2) as the chief reaction product. Similarly, A -androstene-3/3,17/3-diol-16-one is converted into... 

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