5a- Estrane

For the reduction of conjugated enones to saturated alcohols, Procedure 5 (section V) may be modified by adding methanol in place of ammonium chloride a sufficient excess of lithium is present to effect reduction of the intermediate saturated ketone to the alcohol. Procedure 2 (section V) for effecting Birch reductions is also useful for reduction of conjugated enones to saturated alcohols. Thus, 17-ethyl-19-nortestosterone affords crude 17a-ethyl-5a-estrane-3) ,17) -diol of mp 174-181°, reported mp 181-183°, in quantitative yield. 

Occasionally, the parent drug is not excreted in urine at a detectable concoitration, and a knowledge of the m bolic pathways in the particuku species is thus essoitial. An example of this is the identification of 5a-estrane-3p,17a-diol in the urine of horses, or of 19-norandrosterone and 19-nor-etiocholanolone in the urine of humans, to prove administration of the anabolic steroid nandrolone. A few drugs are notable for being excreted in urine almost... 

Major metabolite (glucuronic acid conjugate) 17a-Epimer 5a-Estrane-3) , 17a-diol 5a-Androstane-3) , 17a-diol 17a-Epimer... 

Elute the corresponding area of the chromatographed extract with methanol, separate the silica gel by centrifugation, and evaporate the methanol to dryness in a reaction tube at 60° in a stream of oxygen-free nitrogen. Testosterone, nandrolone, trenbolone, and 5a-estrane-3(3,17a-diol are coeluted with the standard. Boldenone runs below the other substances if its presence is suspected, a reference solution should be included in the chromatography. 

Gas Chromatography-Mass Spectrometry. Prepare methoxime derivatives by heating the extract from the thin-layer chromatographic plate with 100 xl of an 8% solution of methoxyamine hydrochloride in dry pyridine at 60° for 30 minutes, and evaporate in a rotary film evaporator. Silylate by dissolving the residue in 100 Lll of chloroform, adding 100 Lll of A,0-bis(trimethylsilyl)acetamide and 20 Lll of trimethylchlorosilane, then seal, and heat for 2 hours at 60°. When only 5a-estrane-3P,17a-diol is to be confirmed the methoxime formation can be omitted. Prepare a 2-cm column of Sephadex LH-20 in a Pasteur pipette with a cotton wool plug, using a... 

Disposition in the Body. In man, nandrolone is excreted in the urine mainly as the two metabolites, 19-norandrosterone and 19-noretiocholanolone. In the horse, the major metabolites are 5a-estrane-3, 17a-diol, excreted mainly as the glucuronide conjugate, and its 17j5-epimer which is excreted as the sulphate conjugate. 

Similarly la-methyl-17/3-acetoxy-5a -androstan-3-one (D-lOO), la-hydroxy-17/3-acetoxy-5ci -androstan-3-one (D-I07), and la,2a-meth-ylene-17/3-acetoxy-5a-androstan-3-one (D-112) exhibit substantial androgenic and anabolic activities with very favorable anabolic-androgenic ratios. Still, replacement of the 19-methyl group by hydrogen will bring about a large decrease in the androgenic and anabolic activities, i.e., for the compounds la-methyl-17 8-acetoxy-5a-estran-3-one (N-61), la-hydroxy-17/3-acetoxy-5a-estran-3-one(N-62), and la,2a-methylene-17)8-acetoxy-5a-estran-3-one (N-63). 

In addition to the above-described compounds, there are a few other 19-nortestosterone derivatives which display a favorable anabolic-androgenic ratio by having lower androgenic activities and maintaining the anabolic activity of the standard compound 17a-methyl-l 7j8-hydroxy-19-norandrost-2-ene (N-29), 2-cyano-17/3-acetoxy-19-norandrost-2-ene acetoxy-19-norandrost-4-eno[2,3-c ]isoxazole (N-70), 17a-methyl-17/3-hydroxy-19-norandrost-4-eno[2,3-fii]isoxazole (N-76), and I7a-methyl-17/3-hydroxy-5a-estran-3-one (N-90). 

Fig. 13.2. Basic hydrocarbons (I) 5 -gonane, (II) 5a-gonane, (HI) 5 -estrane, (IV) 5a-estrane, (V) 5p-pregnane, (VI) 5a-pregnane, (VII) 5 -androstane, and (VIII) 5a-androstane. (Dorfman and Ungar, 1965.)...

Williams, J. R., Mattei, R L., Abdel-Magid, A., and Blount, J. E, Photochemistry of estr-4-en-3-ones 17(i-hydroxy-4-estren-3-one, 17(i-acetoxy-4,9-estradien-3-one, 17P-hydroxy-4,9,ll-estratrien-3-one and norgestrel. Photochemistry of 5a-estran-3-ones,/. Org. Chem., 51,769,1986. 

Methylnortestosterone 17 a-methyl-5 P-estrane-3a,17P-diol 17a-methyl-5a-estrane-3a,17P-diol... 

In terms of the threshold-substance 5a-estran-3a-ol-17-one (NorA), several aspects need consideration, e.g., pregnancy and bacterial activity. Urinary levels > 2ng/mL represent doping violations, but several studies outlined the elevated production and elimination of NorA throughout gestation as well as the possibility to form NorA from A by demethylation. Hence, careful interpretations of steroid profiles and tests for bacterial activity (for instance, by means of deuterium-labeled A) are carried out. 

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