5a-androst

Other acid-catalyzed exchanges have been reported with cholest-4-ene-3,6-dione (34) which is unstable to alkaline treatment and with 5a-androst-8(14)-en-lS-one which gives in addition to (35) a significant amount of de-conjugated side products. 

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. ... 

A pertinent example is the reduction of 5a-androst-8-en-l 1-one (154) which yields 8 -di-5a-androstan-l 1-one (155) in 93% isotopic purity. Saturation of A -6-keto steroids gives equally good results for labeling the 8/5-position. ... 

A suspension of lithium aluminum deuteride (1.6 g) in dry tetrahydrofuran (60 ml) is added dropwise to a stirred and cooled (with ice-salt bath) solution of 5a-androst-l4-ene-3j3,17j3-diol (179, 1.6 g) and boron trifluoride-etherate (13.3 g) in dry tetrahydrofuran (60 ml). The addition is carried out in a dry nitrogen atmosphere, over a period of 30 min. After an additional 30 min of cooling the stirring is continued at room temperature for 2 hr. The cooling is resumed in a dry ice-acetone bath and the excess deuteriodiborane is destroyed by the cautious addition of propionic acid. The tetrahydrofuran is then evaporated and the residue is dissolved in propionic acid and heated under reflux in a nitrogen atmosphere for 8 hr. After cooling, water is added and the product extracted with ether. The ether... 

A detailed procedure for the use of MCPBA recently appeared in Reagents for Organic Synthesis by Fieser and Fieser. The commercially available MCPBA (Aldrich) is 85% pure the contaminant, m-chlorobenzoic acid, can be removed by washing with a phosphate buffer of pH 7.5. The epoxidation is usually performed as follows a solution of 3 -acetoxy-5a-androst-16-ene (2.06 g, 6.53 mmoles) in 25 ml of chloroform (or methylene dichloride) is chilled to 0° in a flask fitted with a condenser and drierite tube and treated with a solution of commercial MCPBA (1.74 g, 20% excess) in 25 ml chloroform precooled to the same temperature. The mixture is stirred and allowed to warm to room temperature. After 23 hr (or until TLC shows reaction is complete) the solution is diluted with 100 ml chloroform and washed in sequence with 100 ml of 10% sodium sulfite or sodium iodide followed by sodium thiosulfate, 200 ml of 1 M sodium bicarbonate and 200 ml water. The chloroform extract is dried (MgS04) and evaporated in vacuo to a volume of ca. 10 ml. Addition of methanol (10 ml) followed by cooling of the mixture to —10° yields 0.8 gof 16a,17a-epoxide mp 109.5-110°. Additional product can be obtained by concentration of the mother liquor (total yield 80-90%). 

The addition of diazomethane to 17j -hydroxy-5a-androst-l-en-3-one (7) gives the A -pyrazoline (8) in which the C=N bond is conjugated with the 3-keto group. °°... 

To a stirred solution consisting of 5 g (9.45 mmoles) 3, 17) -dibenzoyloxy-5a-androst-7-en-6a-ol in a mixture of 150 ml of dry ether and 150 ml of glyme is added lOg (0.16 moles) of zinc-copper couple and 26.7 (8 ml, 0.1 moles) methylene iodide. The mixture is heated under reflux for 4 hr, cooled to room temperature, diluted with 200 ml of ether and filtered. The filtrate is washed with a saturated solution of sodium chloride and water, and dried over anhydrous sodium sulfate. The ether is removed under reduced pressure and the residue is crystallized from acetone-hexane to yield 4.4 g (86%) of 3, 17 -dibenzoyloxy-7a,8a-methylen-5a,8a-androstan-6a-ol mp 166-167° [ ]d -62° (CHCI3). 

This procedure has been successfully used to homologate l-en-3-ones. Muller and co-workers prepared 17j5-hydroxy-A-homo-5a-androst-l-en-4-one acetate (19a) and 17/ -hydroxy-l-methyl-A-homo-5a-androst-l-en-4-one acetate (19b) from the l-en-3-ones (18a) and (18b), respectively, using diazomethane and aluminum chloride. 

Hydroxy-6-methyl-10 (5 6) abeo-cholestan-5-one acetate, 391 3 a-Hydroxy-16a-methyl-11,20-dioxo-5/3-pregnane-21-glyoxylic acid, 191 17 -Hydroxy-l-niethyl-A-homo-5a-androst-l-en-3-one acetate, 362 17 /3-Hy droxy-5a, 1 Oa-methy lene-A-norestran-3-one, 429 17 3-Hydroxy-17 a-methyl-10 ( 5 4) -fl( < o-estrane-3,5-dione, 314 3a-Hydroxy-16a-methyl-5/3-pregnane-11,20-dione, lyl... 

Chemical Name 17j3-Hvdroxv-1j3-methvl-5a-androst-1-ene-3-one acetate Common Name —... 

Recent results indicate that the air-borne steroids 5a-androst-2-en-17p-ol and 5a-androst-2-en-17-one, which are present in the urine of female E. maximus during the luteal phase at levels that are increased 10- to 20-fold, could be responsible for the synchronization of estrus in females living in close social relationships [117]. The ketone has previously been identified as a product of the incubation of androsterone sulfate with human axillary bacterial isolates [118]. 

Not only the sensitivity of the human olfactory system to androstenol (5a-androst-16-en-3a-ol) and androstenone (5a-androst-16-en-3-one),but also the difference in the sensitivity with which individuals can detect these compounds and the fact that they are implicated in the semiochemical communication of the pig, Sus scrofa [166,167], have led to them being considered human pheromones. Final confirmation that they are human pheromones is still outstanding. However, it was recently found that passive inhalation of another related steroid, androsta-4,16-dien-3-one, can influence the physiological state of humans by increasing a positive mood in test persons [168]. It has yet to be determined whether humans exude concentrations of this chemical information that are adequate for communication within social contexts. 

The well-known boar pheromone was not only one of the first mammalian pheromones identified, but also the first one applied commercially. The saliva from the submaxillaiy gland contains two steroids. These are 5a-androst-16-en-3-one and So -androst-lS-en-So -ol (Fig. 7.8). They are emitted during head-to-head contact in courtship. Both individually stimulate the sow to assume the mating stance, but a mixture of the two is not more active than either compound (Melrose etal., 1971). This may be a case of adaptive redundancy. 

Amoore, J. E., Pelosi, P., and Forrester, L. J. (1977). Specific anosmias to 5a-androst-16-en-3-one and primary odors. Chemical Senses and Flavour 1,401-425. 

Among bicyclic cyclohex-2-enones, the formation of tricyclo[4.4.2.01,6]dodecane-2,7-dione from bicyclo[4.4.0]dec-l(6)-ene-2,7-dione and ethene proceeds in 95% yield,101 and that of 8-mcthyl-tricyclo[6.4.0.01,4]dodecan-5-ones from 6-methylbicyclo[4.4.0]dec-l(2)-en-3-one and ethene in 77% yield,102 respectively. Steroids containing cyclohex-2-enone subunits,103 e.g. 17/ -acetoxy-5a-androst-1 -en-3-one,104 often afford /raw-fused cycloadducts with alkenes. When such reactions are performed on silica gel, complete reversal of stereochemistry to that observed in solution can occur.105... 

The low reactivity of the conjugated steroidal 3-oxo group towards the sulfur tetrafluoride/ hydrogen fluoride reagent is illustrated by the reaction of 5a-androst-1 -enc-3,11,17-trione which gives the 17,17-difluoro steroid 6 (66%) and the 3,3,17,17-tetrafluoro steroid 7 in only 7% yield.72... 

Androst-4-ene-3,ll,17-trione, 88, 377, 409 di-Androst-5-en-3/3-oI, 199 Androst-5-en-17-ol-3-one, 32 Androst-l-en-3-one, 152 Androst-4-en-3 -one, 152 5a-Androst-8-en-l 1-one, 189 5 -Androst-8(14)-en-15-0ne, 155 Anhydrous hydrogen fluoride, 425 Aqueous hydrogen fluoride, 435 Argentic picolinate, 241 17a-aza-D-homo-estrone methyl ether, 163... 

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