5a-Androstane-3a,178-diol

Thin-layer Chromatography. Dissolve the residue in chloroform and apply to a silica gel plate. At the same time apply a solution containing 1 mg/ml of 5a-androstane-3a,17(3-diol in methanol as a reference solution. Develop the plate in a mobile phase consisting of ethyl acetate chloroform (1 1). Spray the reference solution only with a 10% solution of molybdophosphoric acid in methanol. The reference substance appears as a blue-grey spot on a yellow background. 

Cy ano-17- (2 -tetr ahydropyr anyloxy) -androst-5-en-3 -ol acetate, 134 5,19-Cyclo-5a, 10a-androstane-3a, 17/3-diol, 113... 

Compendial reviews state that rocuronium bromide had been identified as having eight different impurities, which are labeled as impurities A, B, C, D, E, F, G, and H. Impurity A (i.e., related compound A) is 3a-hydroxy-2/i (morpholin-4-yl)-16/ -(pyrrolidin-l-yl)-5a-androstan-17/ -yl acetate impurity B (i.e., related compound B) is l-[3a,17/i-bis(acetyloxy)-2/i-(morpholin-4-yl)-5a-androstan-16/i-yl]-l-(prop-2-enyl)pyrrolidinium impurity C (i.e., related compound C) is l-[3a,17/i-dihydroxy-2/i-(morpholin-4-yl)-5a-androstan-16/ -yl]-l-(prop-2-enyl)pyrrolidinium and impurity D (i.e., related compound D) is l-[3a-(acetoxy)-17/J-hydroxy-2/J-(morpholin-4-yl)-5x-androstan-16/j-yl]-l-(prop-2-enyl)pyrrolidinium impurity E (i.e., related compound E) is l-[17/ -(acetoxy)-3a-hydroxy-2/ -(pyrrolidin-l-yl)-5a-androstan-16/)-yl]-l-(prop-2-enyl)pyrrolidinium impurity F (i.e., related compound F) is l-[3a,17/ -bis(acetiloxy)-2/ -(pyrrolidin-l-yl)-5a-androstan-16/i-yl]-l-(prop-2-enyl)pyrrolidinium impurity G (i.e., related compound G) is 2/)-(morpholin-4-yl)-16/i-(pyrrolidin-l-yl)-5a-androstane-3a,17/i-diol and impurity H (i.e., related compound H) is l-[17/i-(acetyloxy)-2-(morpho-lin-4-yl)-3-oxo-57-androst-l-en-16/i-yl]-l-(prop-2-enyl)pyrrolidinium [5-7], The molecular structure of rocuronium bromide is shown in Fig. 6.1, while the structures of the known impurities are illustrated in Fig. 6.2. 

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. 

Testosterone glucuronide can be converted directly into 5/8-androstane-3a,17/3-diol 17-glucuronide (Robel et al., 1966a), and as no 5a reduced... 

Estr-5(10)-ene-3a,17 -diol (10 g, 36.2 mmoles) is added over a period of 1 hr to a refluxing mixture consisting of 60 g (0.92 moles) of zinc-copper couple, 350 ml of dry ether and 180 g (54 ml, 0.67 moles) of methylene iodide. After the addition is complete, half of the solvent is removed by distillation and 200 ml dry ether is added. The reaction mixture is then transferred to a sealed stainless steel tube and maintained for 3 hr at 92° before being cooled in an ice bath and poured into 500 ml of saturated aqueous sodium bicarbonate solution. The resultant mixture is extracted with ether and the extracts are dried over anhydrous sodium sulfate and concentrated to yield a solid residue which gives 8.4 g (80%) 5,19-cyclo-5a,10a-androstane-3a,17) -diol mp 161-163° [aJo 40° (CHCI3), on crystallization from acetone. 

A solution of sodium borohydride (8 grams) in water (16 ml) was added to a stirred solution of 2(3,16(3-bis-piperidino-5a-androstan-3a-ol-17-one (17 grams) in tetrahydrofuran (70 ml) and methanol (30 ml) and the solution stirred at room temperature for 16 hours. The product was precipitated by the addition of water, filtered off, dried, and crystallized from acetone to give the diol (14.9 grams). 

Solv. Ref. C- 5a-Andro- 5a-Andro- 5a-Andro- 5a-Andro- 5a-Androstan- 5a-Androstane- 5a-Androstane-stan-16 -o1 stan-16j8-ol stan-17a-ol stan-17/J-ol 3,17-dionc 3a,17/i-diol 3/7,17/ -diol CDC13 CDCI3 CDCI3 CDCI3 CDCI3 Pyridine Pyridine [575] [575] [575] [575] [564] [273] [273] Androst-4-ene-3,17-dione CDCU/Dioxane [65 a]... 

Ryan DE, Dixon R, Evans RH, Ramanathan L, Thomas PE, Wood AW, Levin W (1984) Rat hepatic cytochrome P-450 isozyme specificity for the metabolism of the steroid sulfate, 5a-androstane-3a,17P-diol-3,17-disulfate. Arch Biochem Biophys 233 636-642... 

List of abbreviations and trivial names. Dehydroepiandrosterone (DHA, D), 3/J-hydroxyandrost-5-en-17-one androstenediol (A°-diol, A ), androsta-5-en-3/S, 17 -diol androstenetriol (triol), androsta-5-en-3, 16o, 17 -triol androsterone (A), 3ot-hy-droxy-5a-androstan-17-one 5/S-androsterone (5fiA), 3a-hydroxy-5/3-androstan-17-one epiandrosterone, 3/3-hydroKy-5o-androstan-17-one androstanediol (Adiol), 5a-and-rostan-3a, 17/S-diol 3/S-androstanediol, 5a-androstan-3/9, 17/3-diol 5/3-androstanediol (5 Adiol), 5/S-androstan-3a, 17 -diol androstenedione (A ), androsta-4-en-3, 17,... 

Hydroxy-l7a-methyl-2-oxa-5a-androstan-3-one, 41B, 592 2,4-Dioxa-5a-androstan-17/3-ol acetate, 41B, 593 14p-Azido-5a-androstane, 40B, 486 3a, 17/J-Dihydroxy-5a-androstane, 38B, 531 5/3-Androstane-3a, 1 7 -diol, 37B, 295 17/3-Hydroxyandrostan-3-one monohydrate, 38B, 532 3/3,17/3-Dihydroxy-5a-androstane monohydrate, 39B, 382... 

A number of steroids have been regioselectively acylated ia a similar manner (99,104). Chromobactenum viscosum hpase esterifies 5a-androstane-3P,17P-diol [571-20-0] (75) with 2,2,2-triduoroethyl butyrate ia acetone with high selectivity. The hpase acylates exclusively the hydroxy group ia the 3-position giving the 3P-(monobutyryl ester) of (75) ia 83% yield. In contrast, bacillus subtilis protease (subtihsia) displays a marked preference for the C-17 hydroxyl. Candida iylindracea]i 2Lse (CCL) suspended ia anhydrous benzene regioselectively acylates the 3a-hydroxyl group of several bile acid derivatives (104). 

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