Mono-oxygenated pregnanes

A-ring conjugated ketones do not normally interfere with the epoxidation reaction, but hydride reduction will reduce any ketone groups to alcohols. These can be reoxidized by conventional means. 

Reduction of 17a-EthynyI to 17a-Ethyl °° A solution of 5 g of 17a-ethynyl-androst-5-ene-3j9,17j5-diol in 170 ml of absolute alcohol is hydrogenated at atmospheric pressure and room temperature using 0.5 g of 5 % palladium-on-charcoal catalyst. Hydrogen absorption is complete in about 8 min with the absorption of 2 moles. After removal of the catalyst by filtration, the solvent is evaporated under reduced pressure and the residue is crystallized from ethyl acetate. Three crops of 17a-ethylandrost-5-ene-3) ,17j9-diol are obtained 3.05 g, mp 197-200° 1.59 g, mp 198.6-200.6° and 0.34 g, mp 196-199° (total yield 5.02 g, 90%). A sample prepared for analysis by recrystallization from ethyl acetate melts at 200.6-202.4° [aj, —70° (diox.). 

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°. 

Reductive Opening of a 17a,20-Epoxide 17a,20-Oxidopregn-4-en-3-one (0.7 g) in 90 ml of dioxane (previously distilled over sodium) is added gradually to a solution of 1 g of lithium aluminum hydride in 50 ml of dry ether. 

The mixture is distilled until most of the ether has been removed and then refluxed for 8 hr. Ethyl acetate is added to decompose the excess reagent and concentrated aqueous sodium sulfate is then added until the precipitate begins to adhere to the sides of the flask. Finally ca. 100 g of solid sodium sulfate is added, the salts are removed by filtration and washed well with dioxane. Evaporation of the solvent gives a solid residue which is dissolved in 60 ml of chloroform and shaken with 3.5 g of manganese dioxide for 16 hr. Subsequently another 3.5 g of manganese dioxide is added and shaking continued for a further 16 hr. The solid is removed by filtration and washed well with hot chloroform. Evaporation of solvent and crystallization of the residue from acetone-hexane affords 0.51 g (72%) of 17a-hydroxy-17jff-ethylandrost-4-en-3-one mp 145-148°. 

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The addition of ethoxyacetylene to 17-keto steroids has been discussed earlier. The 17a-ethoxyethynyl-17jS-hydroxy compounds thus produced can be readily converted to 21-mono-oxygenated pregnanes by acid treatment. 

Preparation of 20-monO-oxygenated pregnanes by side-chain oxygenation of pregnanes... 

IV. Side-Chain Oxygenation of Pregnanes / 162 17-Mono-oxygenated pregnanes / 162... 

B) Derivatives of 3,20a-diamino-5a-pregnane with oxygen at C-4. Terminaline, a mono-amino-derivative, belongs to this latter type. 

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