5a- Pregnane

Deuteration at C-3 by Lithium Aluminum Deuteride Reduction of 5a.-Pregnane-3,20-dione 3-Tosylhydrazone 20-Ethylene keta ... 

Acetoxy-17a-hydroxy-5a-pregnane-3,l 1,20-trione (40) is brominated in acetic acid under equilibrating conditions to give a solution of the 2a,4a-di-bromo compound (41). This is reduced by chromous chloride without further treatment, to the 4a-bromo compound (42). The recrystallized bromo compound (42) is then dehydrobrominated via the semicarbazone (43) which is converted without isolation into cortisone acetate (44) by treatment with pyruvic acid ... 

Selectivity in formation of protective groups may also be achieved by a proper choice of reaction conditions and catalyst. Thus formation of the 3-monothioketal from 3,6-diketones is achieved by dilution of the ethane-dithiol-boron trifluoride reaction mixture with acetic acid. 3-Monocyanohydrins are obtained in good yield from 3,20-diketo-(5a)-pregnanes by diluting the exchange reaction with ethanol. Similarly, dilution of the... 

Cyano-3 -hydroxy-5a-pregnan-20-one A suspension of 5a-pregnane-3, 20-dione (2 g) in ethanol (90 ml) is treated with acetone cyanohydrin (4 ml) and three drops of triethylamine and stirred at room temperature until complete dissolution. After 3 hr, the solution is diluted with 200 ml of water, acidified with acetic acid and the crystalline precipitate is thoroughly washed with water and dried under vacuum to give 2.1 g (97%) of product mp 172-178° (dec). A sample recrystallized from ethyl acetate melts at 176-179° (dec) [a]p 86° (ethyl acetate). 

Deuteration at C-3 by lithium aluminum deuteride reduction of 5a-pregnane-3, 20-dione 3-tosylhydrazone 20-ethylene ketal, 177... 

A total of 50 ml (0.15 moles) of a 3 ethereal solution of methylmagnesium bromide is added slowly to a vigorously stirred solution of 5.8 g (12.5 mmoles) or 3,3 20,20-bisethylenedioxy-5a,6a-epoxy-5a-pregnane-ll/l,17a,21-triol in 400 ml of tetrahydrofuran. The solution is heated under reflux for 24 hr, cooled and treated with 32 ml of saturated ammonium chloride solution. The supernatant is decanted and the residue is washed with several portions of tetrahydrofuran. The combined supernatants are evaporated and extracted with ethyl acetate, washed with saturated salt solution, dried and concentrated to give 4,55 g (75%) of 3,3 20,20-bisethylenedioxy-6 -methyl-5a-pregnane-5a,ll, 17a,21-tetrol mp 170-172° after crystallisation from acetone-petroleum ether. The analytical sample is crystallized from acetone-petroleum ether mp 175-177° [aJo —11° (CHCI3). 

The enamine (1 g) in 30 ml of benzene and 5 ml of toluene is treated, with cooling, with a solution of 0.33 g (1.04 eq.) of perbenzoic acid in 2.1 ml of benzene. The reaction is complete in a few minutes. Ether (30 ml) is added, then the solution is washed with 2 N sodium hydroxide and with water to neutrality, dried over sodium sulfate and evaporated under reduced pressure. Crystallization from acetone gives 0.51 g of crude product mp 230°. One further crystallization from methanol gives 0.38 g (50%) of 3J5,17a-dihydroxy-5a-pregnan-20-one rap 265°. 

A solution of 50 g of 3 -acetoxy-16 -methyl-5a-pregnan-20-one in tetrahydrofuran (120 ml) is added over 5 to 10 min, the passage of oxygen being continued for a further 45 min while maintaining the temperature at... 

The oxygen is then replaced by nitrogen and a solution of sodium hydroxide (5 g) in methanol (100 ml) and water (50 ml) is added. After agitation for 70 min at ambient temperature, followed by the addition of acetic acid (10 ml), the mixture is poured into water (4 liters). The precipitate is isolated by filtration, washed with water and dried in an air draft at 100° to yield 47 g of crude product. This material is dissolved in methanol (1.5 liters) and ethyl acetate (500 ml) and the solution concentrated to half its initial volume. Ethyl acetate (500 ml) is added and the solution is cooled to yield 29.4 g (63%) of 3, 17a-dihydroxy-16f -methyl-5a-pregnan-20-one mp 255-260° [ajp 45.6° (diox.). 

---