5-a-Androstan-17-one

Fig. 6.12. Gradient CEC separation of derivatized neutral steroids. (Reprinted with permission [38], Copyright 2000 Elsevier). Conditions Column 35 cm (active length 25 cm) x 100 pm i.d., mobile phase gradient of acetonitrile-water-240 mmol/L phosphate buffer pH 3 from 35 60 5 to 65 30 50 in 15 min 600 V/cm injection 100 V/cm for 10 s. Peaks labeling reagent 1, progesterone 2, 11 P-hydroxyandrosterone 3, dehydroisoandrosterone and equiline 4, estrone 5, androsterone 6, 19-hydroxy-4-androsterone-3,17-dione 7, 5-a-androstan-17-one 8.

Wu et al. have reported that direct excitation of amines in the presence of 3, y -hydroxy-5-a-androstan-17-one, under conditions where light is exclusively absorbed by the amine leads to the reduction of the 17-keto group with high stereoselectivity (Scheme 83) [340]. 

Dihydro-A-nortestosterone, 35 Dihydropyridylaluminum hydride, 75 3 a, 6a-Dihydroxy-5 /3-androstan-17-one, 415 3 a,6o -Dihydroxy-5j8-androstan- 17-one dinitrate, 415... 

Treatment of the 4-oxasteroid 467 with Lawesson s reagent effects the simultaneous O—>S conversion and dehydration of the hemiacetal unit to give the 4-thia-5-androstene-17-one in 40% yield. Subsequent hydrogenation results in a (3 2) mixture of the 4-thia-5-ot- and 5-(3-androstane-17-ones (Scheme 161) <2005T3691>. 

The fused pyrrole ring system (204) has been obtained by the reaction of 17/3-hydroxy-17-methylandrosta-l,4-dien-3-one with tosylmethyl isocyanide in the presence of sodium hydride in DMSO,92 and 17/3-hydroxy-17-methyl-7-oxa-5o -androstano-[3,2-c]- (205) or -[2,3-d]-isoxazoles (206 X = O) have been prepared by treating 7-oxa-2-(hydroxymethylene)-17/3 -hydroxy-17-methyl-5 a -androstan-3-one with hydroxylamine hydrochloride.93 In the presence of pyridine, the isox-azole (206 X = O) is formed, but when the reaction is catalysed by sodium acetate in acetic acid the isomeric steroid (205) results. Cycloaddition of hydrazine hydrate to the same 2-hydroxymethylene-7-oxa-steroid results in the [3,2-c]pyrazole (206 X = NH). A similar addition is encountered in the reactions between 3/3-hydroxy-16-(hydroxymethylene)-5a-androstan-17-one and the substituted hydrazines RNHNH2 (R = H, o-COC6H4NH2, or p-COQHUNH ,) when the corresponding [17,16-c]pyrazoles (207) are formed after cyclization of the intermediate hydrazones.94... 

HYDROXY-2-HYDROXYMETHYLENE-17-a-METHYL-3-ANDROSTANONE 17-P-HYDROXY-2-(HYDROXY-METHYLENE)-17-METHYL-5-a-ANDROSTAN-3-ONE ... 

HYDROXYMERCURY)PROPYL)C,MlBAMOYL)PHEN OXY)ACETIC ACID see NCM800 17-p-HYDROXY-2-HYDROXYMETHYLENE-17-a-METHYL-3-ANDROSTANONE see PANIOO 17-p-HYDROXY-2-(HYDROXYMETHYLENE)-l 7-a-METHYL-5-a-ANDROSTAN-3-ONE see PANIOO 17-P-HYDROXY-2-(HYDROXYMETHYLENE)-17-METHYL-5-a-. NDROSEMSI-3-ONE see PANIOO 17-HYDROXY-2-(HYDROXYMETHYLENE)-17-METHYL-5-a-17-P-ANDROSTAN-3-ONE see PANIOO... 

HYDROXYMETHYLENE-17-a-METHYL-5-a-ANDROSTAN-17-P-OL-3-ONE see PANIOO 2-HYDROXYMETHYLENE-l 7-a-METHYL-DIHYDROTESTOSTERONE see PANIOO 2-(HYDROXYMETHYLENE)-17-a-METHYLDIHYDROTESTOSTERONE see P.ANIOO 2-HYDROXYMETHYLENE-17-a-METHYL-17-P-HYDROXY-3-ANDROSTANONE see PANIOO 4-(l-HYDROXY-2-((l-METHYLETHYL)AMINO)ETHYL)-l, 2-BENZENEDIOL see DM "600... 

Treatment of the epoxy sulfones obtained thus with MgBr2 produces a-bromo ketones or a-bromo al-dehyde. This conversion can be applied to stereoselective preparations of a-bromo methyl ketones from cyclohexanone derivatives. Thus, treatment of 17-P-hydroxy-5-a-androstan-3-one (134) with 1-chloroethyl phenyl sulfone provides an epoxy sulfone (135), which is cleaved by MgBr2 to give a 99 1 mixture of 3-acetyl-3-bromoandrostanes (136 and 137 equation 33), whereas similar treatment of 17-p-hydroxy-5-B-androstan-3-one (138) gives a 4 96 mixture of 3-acetyl-3-bromoandrostanes (139 and 140 equation 34). These facts may reflect the steric course of the initial attack of the a-sulfonyl carbanion on the carbonyl face. 

Bruchovsky N, Wilson JD. The conversion of testosterone to 5-a-androstan-17-P-ol-3-one by rat prostate in vivo and in vitro. J Biol Chem 1968 243 2012-2021. 

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,... 

The testosterone enzyme immunoassay was a solid phase double antibody competitive inhibition assay with horseradish peroxidase linked to testosterone-3-CMO. The testosterone antiserum was generated in rabbits against 4-androsten-ll-a-17-p-diol-3-one-ll-hemisuccinate bovine serum albumin. Cross reaction of the antiserum was as follows 17-p-hydroxyl-4,6-androstandien-3-one (60%), 5-a-androstan-17-p-ol-3-one (52%), 19-... 

A mixture of 17j -acetoxy-2a-bromo-5a-androstan-3-one refluxed 14 hrs. with excess n-propyl mercaptan in chloroform under Ng, solvent and excess mercaptan removed in vacuo, the residue stirred and refluxed 4 hrs. in aq.-methanolic HCl, the resulting n-propyl mercaptan and disulfide removed hy co-distillation with water in vacuo, the crude product mixture reacetylated hy heating 1 hr. with acetic anhydride and pyridine, finally the 3-ketone removed as its bisulfite addition product after treatment of the mixture with aq. Na-metabisulfite in boiling methanol 17j -acetoxy-5-a-androstan-2-one. Overall Y 41.5%.—Reduction of the intermediate 2,3-bis-(n-propylthio)-5a-androst-2-en-17/ -ol acetate by n-propyl mercaptan occurs only under strongly acidic conditions and in a random manner to produce the 2- and 3-n-propylthio derivatives in essentially equal quantities. The 3-ketone forms a bisulfite addition product under conditions where the 2-ketone does not react at all. Hydrolysis of the addition product affords a 49% yield of the 3-ketone, which can be used again. R. L. Clarke, J. Org. Chem. 28, 2626 (1963). 

An example is the preparation of 18-trideuterio 5a-steroids bearing a side chain at C-17. Labeling of this position with three deuteriums was accomplished by utilizing the Johnson procedure for steroid total synthesis. This synthesis involves, in part, introduction of the 18-angular methyl group by methylation of the D-homo-17a-keto-17-furfurylidene intermediate (243). By substituting d3-methyl iodide in this step, the C/D cis- and ra/J5-18,18,18-d3 labeled ketones [(244) and (245)] are obtained. Conversion of the C/D tra 5-methylation product (245) into 18,18,18-d3-d /-3)8-hydroxy-5a-androstan-17-one (246) provides an intermediate which can be converted into a wide variety of C-18 labeled compounds of high (98%) isotopic... 

Vinyllithium Reaction To a cooled solution of 80 g of 3y -hydroxy-5a-androstan-17-one in 1.5 liters of tetrahydrofuran is added 400 ml of 2 4/ vinyllithium in tetrahydrofuran. The solution is stirred at 0° for 0.5 hr, allowed to warm to room temperature, and stirred an additional hr. Cone ammonium chloride solution is added, and the mixture is concentrated under reduced pressure until a precipitate begins to form. The slurry is poured into water, and the precipitate is filtered and recrystallized twice from methanol, affording 52.2 g (60%) of 17a-vinyl-5a-androstane-3, 17i -diol mp 205-207.5°. 

Overall yields of 37% from pregnenolone acetate to 19-norprogesterone and of 43% from 3 -acetoxy-5a-chloro-6l5-hydroxy androstan-17-one to A io)-19-norandrostene-3,17-dioneii have been reported using 6)5,19-ethers as key intermediates. 

Acetylenedimagnesium bromide, 66, 84, 137 Acyl-alkyl diradical disproportionations, 299 Acyl-alkyl diradical recombination, 296 Alkaline hydrogen peroxide, 10, 12, 20 Alkylation of formyl ketones, 93 Alkylation via enolate anions, 86 17a-Alkynyl steroids from 17-ketones, 67 2a-Al]yl-17jS-hydroxy-5a-androstan-3 -one, 9 5 Allylic acetoxylation, 242 Allylmagnesium bromide, 64 17 -Aminoandrost-5-en-3 -ol, 145 17 a-Aminomethy 1-5 a-androstane-3, 1718-diol, 387... 

Hydroxy-16/3,17 /3-ethylene-17 a-pregn-5-en-20-one acetate, 349 17/3-Hydroxy-A-homo-5/3-androstan-4-one, 359... 

A solution of 1.0 g of 3,17-androstandione in 50 ml of methanol and containing 1 g of selenium dioxide, was allowed to remain in an ice-chest overnight. The formed 3,3-dimethoxy-androstan-17-one was not separated. 1 g of solid potassium hydroxide and 2.5 g of sodium borohydride in 2.5 ml of water were added and the mixture allowed to react at room temperature for 24 hours. The solution was then poured into a large excess of water, extracted... 

A-Nor-5.alpha.-androstan-3-one, 17.b. -hydr oxy-5-vinyl-, acetate (8CI) P ocarpa-8,11, 13-triene-3.beta.,12-diol, 13-isopropyl-, diacetate (8CI)... 

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