12-Ketocholane

The first application of the manifold experiences gained in the field of bioreductions to substances of the cholic acid and sterol series is due to Kim. He showed that dehydrodesoxycholic acid is transformed by bottom yeast to 3-hydroxy-12-ketocholanic acid. Mamoli and Vercel-... 

Stereoselective reduction. 12-Ketocholanic acids are reduced by this complex to 12/ - and 12a-hydroxycholanic acids in ratios of 5.0 1.5. 3-Keto- and 7-ketocholanic acids are reduced with some preference to the a-hydroxy acids. 

Inversion of 3 -hydroxy steroid. Reduction of the dihydroxy keto cholanate 1 with Raney nickel (no. 28) results in partial epimerization of the axial 3 -hydroxy group (but not the axial 7a-group). This inversion step must be fairly slow because it is not observed when reduction of a 12-ketocholanic acid group is effected within 4 hours. This reaction is the mildest method known for inversion of an axial C,-slcroidal alcohol. ... 

Dehydrogenation of carbonyl compounds. Introduction of a 9,11-double bond into a 12-keto bile acid by selenium dehydrogenation was discovered by Schwenk and Stahl and became a key step in the commercial production of cortisone. Kendall and co-workers " studied the reaction carefully as applied to methyl 3a-benzoyloxy-12-ketocholanate, using as solvent a 4 1 mixture of chlorobenzene and acetic acid. They found that a trace of hydrochloric acid slowed down the reaction but increased the yield. Thus with no added mineral acid the yield reached a maximum of 67% in a reflux period of 24 hrs. but with the mixture 0.0006 normal in HCl refluxing for 72 hrs. alforded the product in 84% yield. The product was to be isolated after... 

Bromination. BF3-OEt2 can catalyze the bromination of steroids that cannot be brominated in the presence of HBr or sodium acetate. Hence, 1 la-bromoketones are obtained in high yields from methyl 3o, 7o -diacetoxy-12-ketocholanate. Bronii-nation (at the 6o -position) and dibromination (at the 6a - and 1 lo -positions) of methyl 3o -acetoxy-7,12-dioxocholanate can occur, depending on the concentration of bromine. ... 

One of the simplest and most efiicient processes for accomplishing the shift of the C-12 oxygen function to C-11 is due to Gallagher. Methyl desoxycholate (Fig. 1) upon partial acetylation at C-3 and oxidation at C-12 leads readily to methyl 3a-acetoxy-12-ketocholanate (I). Bromination... 

To a solution of 5.95 g 3-hydroxy-12-ketocholanic acid in 50 mL methanol was added 2 mL acetyl chloride. The solution was refluxed for 15 min and then allowed to stand at room temperature for 3 h. The ester was obtained in crystalline form by carefully diluting the solution to 175 mL with water, in the amount of 5.10 g (99% yield), m.p., 110-112°C. 

A sample of 7.2 g of the crude 3-hydroxy-12-keto-nor-cholanyldiphenylcarbinol dissolved in 50 mL acetic acid and 25 mL acetic anhydride was refluxed for 2.5 h. The solvent was removed by vacuum distillation, and the gummy residue was dissolved in hot acetone. On standing in the cold room, 1.454 g 3-acetoxy-12-keto-bis-nor-cholanyldiphenylethylene was separated as crystals, in a yield of 24% (based on methyl 3-hydroxy-12-ketocholanate), m.p. 175-178°C... 

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