5a-Androstan-17-one

The reaction of 6-amino-5-(l,2-diethoxycarbonylhydrazino)pyrimidines with enamines represents another convenient method for the preparation of pteridines. Fusion of 5-(l,2-diethoxycarbonylhydrazino)-2,4,6-triaminopyrimidine (281) with an excess of mor-pholinocyclohexene leads to 2,4-diaminotetrahydrobenzo[g]pteridine, and with the morpholinoenamine (282) from 17/3-hydroxy-5a-androstan-3-one regioselective condensation to the fused pteridine (283) takes place in almost quantitative yield (equation 101) (71CC83). 6-Amino-5-nitroso- and 6-amino-5-phenylazo-pyrimidines react similarly, imitating the Timmis-type reaction (72CPB1428). 

Enolizalion of conjugated or /3,y-unsatiirated enones and dienones in O-deiiterated solvents facilitates the introduction of deuterium labels into positions as far as three and five carbon atoms away from a given ketone function. Exchange of the activated hydrogens in androst-4-en-3-one (12) provides a good illustration of the potential of this method. Saturation of the double bond (section V) in the deuterated enone (13) followed by back exchange of the a-deuteriums (section II-B) proves to be an excellent method for the preparation of 6,6-d2-5a-androstan-3-one (15). ... 

Deuteration at C-3 by Reduction of 5a.-Androstan-3-one Oxime with Lithium Aluminum Deuteride... 

A solution of 5a-androstan-3-one oxime (112 0.6 g) in dry ether (40 ml) is added dropwise to a boiling suspension of lithium aluminum deuteride (1.6 g) in dry ether (80 ml). The reaction mixture is heated under reflux for... 

A solution of 4,4-dimethyl-5a-androst-l-en-3-one (128, 14 mg) in cyclohexane (3 ml) is stirred in a microhydrogenation apparatus in the presence of 10 % palladium-on-charcoal (15 mg) at atmospheric pressure and room temperature. The uptake of one eq of deuterium (1.15 ml) is complete in about 1 min and no more deuterium is consumed. After 5 min the catalyst is removed by filtration, and the solvent evaporated under reduced pressure. The resulting l<, 2< -d2-4,4-dimethyl-5a-androstan-3-one (129, 13 mg, 93%), mp 120-122°, exhibits 87% isotopic purity and 13% d species. ... 

When the l<, 2( -d2-labeled product (129) is subjected to alkaline equilibration to back exchange the 2i -label (for experimental conditions see section IT-B), the crystalline l< -di-4,4-dimethyl-5a-androstan-3-one (130) exhibits 6% do and 94% d isotopic composition. ... 

Treatment of 17,17-ethylendioxy-5a-androstan-3-one (10) with ethyl-magnesium bromide affords 11% of the 3a-ethyl epimer (Ha) and 14% of the 3j5-ethyl epimer (12a). 

A total of 3 g (0.13 moles) of sodium hydride is added to a solution consisting of 10 g of 17 -hydroxy-5a-androstan-3-one (36 mmoles) in 200 ml of benzene and 10 ml of ethyl formate. The reaction mixture is allowed to stand under nitrogen for 3 days followed by dropwise addition of 10 ml of methanol to decompose the excess of sodium hydride. The solution is then diluted with 300 ml water and the layers are separated. The basic aqueous solution is extracted with ether to remove neutral material. The aqueous layer is acidified with 80 ml of 3 A hydrochloric acid and the hydroxymethylene steroid is extracted with benzene and ether. The combined organic extracts are washed with water and saturated sodium chloride solution and then dried over magnesium sulfate and concentrated. The residue, a reddish-yellow oil, crystallized from 10 ml of ether to yield 9.12 g (83%) of 17 -hydroxy-2-hydroxymethylene-5a-androstan-3-one mp 162-162.5°. Recrystallization from chloroform-ether gives an analytical sample mp 165-165.5° [a]o 53° (ethanol) 2 ° 252 mjj. (g 11,500), 307 m u (e 5,800). 

A mixture of 3.18 g (10 mmoles) of 17 -hydroxy-2-hydroxymethylene-5a-androstan-3-one, 20 ml dry dimethyl formamide and 0.3 g (13 mmoles) of sodium hydride is stirred for 0.5 hr at room temperature under nitrogen. A total of 1.51 g (12.5 mmoles) of redistilled allyl bromide is added and the mixture is stirred for 1 hr on the steam bath. Aqueous potassium hydroxide (2 g in 5 ml of water) is added and stirring is continued for 1 hr on the steam bath. The reaction mixture is diluted with 50 ml of methylene dichloride followed by careful addition of 300 ml of water. The organic phase is separated and the aqueous phase is again extracted with 50 ml of methylene dichloride. The combined extracts are washed with water, dried over sodium sulfate, filtered and chromatographed on 200 g of silica gel. Elution with pentane-ether (4 1) provides 2a-allyl-17j -hydroxy-5a-androstan-3-one 0.85 g (26%) mp 118-119° [aj 14° (CHCI3), after crystallization from ether-hexane. 

The preparation of 17j -hydroxy-4a-methyl-5a-androstan-3-one (3) which cannot be obtained by direct alkylation or via formyl or oxalyl ketones was achieved by Schaub in 40% yield by the Stork " alkylation procedure. As discussed in the introduction this method proceeds by trapping the A -enolate (2), obtained from (1) and lithium in liquid ammonia, with methyl iodide. 

Treatment of 4-methyltestosterone under the same conditions affords 17 -hydroxy-4,4-dimethyl-5a-androstan-3 One in about 60% yield while 17jS-hydroxyandrosta-4,6-dien-3-one gives only a low yield of 17 -hydroxy-4,4-dimethylandrost-5-en-3-one. ... 

Jones and Price"" therefore concluded that diazomethane ring enlargement of 17j5-hydroxy-5a-androstan-3-one (Ic) proceeds with predominately C3—C4. migration, in contrast to the 5a-cholestane series which differs from (Ic) only in the 17-substituent. 

B-Homosteroids were first reported by Ringold in the course of an investigation of the relationship of structural changes to biological activity of anabolic agents. The Tiffeneau rearrangement sequence described earlier for the preparation of A-homosteroids was used to synthesize 17/ -hydroxy-B-homo-5a-androstan-3-one (56a). 

Oxidation of 17j5-acetoxy-5a-androstan-3-one (1) by chromium trioxide in acetic acid at 55-65° gives the 2,3-seco acid (2). Conversion of the seco acid to its anhydride followed by pyrolysis and distillation gives the A-nor-2-ketone (3) in 45% overall yield. Analogous reactions have been carried... 

Cyanogen azide is a useful reagent for conversion of pyrrolidine enamines of 3-keto steroids to A-norsteroids. " Ring contractions can be carried out in the presence of 17j5-hydroxy, 17j -acetoxy, 20-keto groups and isolated double bonds. In a typical procedure, 17j -hydroxy-5a-androstan-3-one (partial formula 8) is converted into the enamine (9) by pyrrolidine in benzene... 

A solution of 30 g (0.1 mole) of 17j5-hydroxy-5a-androstan-3-one (androstano-lone), 20 ml of pyrrolidine and 200 ml of benzene is heated at reflux temperature for 2.5 hr under a Bidwell-Sterling water trap. The benzene solution is evaporated to dryness in a rotating evaporator connected to a water aspirator. The white cake which remains is broken up and dried further by immersing the flask in a water bath at 60-75° and evacuating the flask with a mechanical vacuum pump. After 0.5 hr the solid cake is broken up again and dried for another 0.5 hr at 60-75°. The enamine (9) obtained should smell only faintly of pyrrolidine. 

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... 

D-homosteroids, 382 Hydrazoic acid, 27, 145 Hydriodic acid, 172 Hydroboration, 165, 166 Hydrogen peroxide, 221 Hydrogen transfer, 239 17 i3-Hydroxy-2-acety l-5a-androstan-3 -one acetate, 342... 

Chemical Name 17/3-hydroxy-1a-methyl-5a -androstan-3-one Common Name —... 

An aqueous slurry of 6 parts of 17/3-hydroxy-17a -methyl-1-oxo-1,2-seco-A-nor-5a -androstan-2-oic acid in 200 parts of water is made alkaline to pH 10 by the addition of dilute aqueous sodium hydroxide, then is treated with 6 parts of sodium borohydride. This mixture is allowed to react at room temperature for about 3 hours. Benzene is added and the resulting mixture is acidified carefully with dilute hydrochloric acid. The benzene layer is separated, and the aqueous layer is further extracted with benzene. The combined benzene extracts are washed successively with aqueous potassium bicarbonate and water, dried over anhydrous sodium sulfate, then evaporated to dryness in vacuo. The resulting residue is triturated with ether to afford pure 17/3-hydroxy-17a -methyl-2-oxa-5a -androstan-3-one,... 

QH7Br02 2491-36-3) see Neticonazole hydrochloride 2P bromo-17p-hydroxy-5a-androstan-3-one (C]yH2yBr02 18000-70-9) see Mesterolone... 

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