Methods for the purification of deoxycholic acid

Abstract

Synthetic methods for preparing deoxycholic acid and intermediates thereof, high purity synthetic deoxycholic acid, compositions and methods of use are provided. Also, provided are processes for the synthesis of 12-keto or 12-α-hydroxy-steroids from Δ-9,11-ene, 11-keto or 11-hydroxy-β-steroids. This invention is also directed to novel compounds prepared during the synthesis. This invention is also directed to the synthesis of deoxycholic acid starting from hydrocortisone.

1 - 14 . (canceled) 
     
     
         15 . A process for preparing a 12-keto compound 3: 
       
         
           
           
               
               
           
         
         from the corresponding Δ-9,11-ene compound 4: 
       
       
         
           
           
               
               
           
         
         where Pg is a hydroxyl protecting group, R is hydrogen, hydroxyl, or —OPg, R 1  is the 17-side chain of a bile acid, which bile acid is selected from the group consisting of cholic acid, deoxycholic acid, taurocholic acid, and glycocholic acid, wherein the carboxyl functionality of said side chain is optionally esterified with a C 1 -C 6  alkyl group, and R 2  is hydrogen, or R 1  and R 2  together with the carbon atom attached thereto form a keto group or a keto protecting group; 
         said process comprises: effecting allylic oxidation at the 12-position of compound 4 wherein the allylic oxidation is effected by a more than one equivalent of tert-butyl hydroperoxide and in the presence of CuI, to first provide a mixture of compounds 1, 2 and 3: 
       
       
         
           
           
               
               
           
         
         and optionally wherein compound 2 is further oxidized to provide the Δ-9,11-ene-12-one compound 3. 
       
     
     
         16 . A process for preparing a 12-keto compound 3: 
       
         
           
           
               
               
           
         
         from the corresponding Δ-9,11-ene compound 4: 
       
       
         
           
           
               
               
           
         
         where Pg is a hydroxyl protecting group, R is hydrogen, hydroxyl, or —OPg, R 1  is the 17-side chain of a bile acid, which bile acid is selected from the group consisting of cholic acid, deoxycholic acid, taurocholic acid, and glycocholic acid, wherein the carboxyl functionality of said side chain is optionally esterified with a C 1 -C 6  alkyl group, and R 2  is hydrogen, or R 1  and R 2  together with the carbon atom attached thereto form a keto group or a keto protecting group; 
         said process comprises: 
         effecting allylic oxidation at the 12-position of compound 4 by reaction with an alkylhydroperoxide of the formula (R 3 )(R 4 )(R 5 )C—O—OH in the presence of a co-oxidant, wherein each of R 3 , R 4 , and R 5  is independently C 1 -C 3  alkyl, wherein the co-oxidant is selected from the group consisting of aqueous sodium hypochlorite, palladium on carbon, Pd(OCOCF 3 ) 2 , Pd(OAc) 2  and CuI, to first provide a mixture of compounds 1, 2 and 3: 
       
       
         
           
           
               
               
           
         
         and optionally wherein compound 2 is further oxidized to provide the Δ-9,11-ene-12-one compound 3. 
       
     
     
         17 - 64 . (canceled)