Efficient synthesis of cholic acid derivates through stereoselective C-H functionalization from hyodeoxycholic acid

Five cholic acid derivatives (including allo-ω-muricholic acid and CDCA) were synthesized from hyodeoxycholic acid via selective oxidation of C3- or C6-hydroxyl groups by IBX and NBS oxidants and stereocontrolled conversion. The hydroxyl group could be introduced through hydrolyzing α-Br keto with K₂CO₃ aqueous solution or through oxidizing the double bond by monoperoxyphthalic acid. The reduction of C6-O6 carbonyl to methylene could undergo with PTSH, NaBH₃CN and ZnCl₂ only at 5β configuration. A feasible synthetic route of CDCA from HDCA has been established to avoid the epimerization with the yield of 45% (8 steps). These strategies provided good yields, stereoselectivity and reproducibility for the preparation of cholic acid derivates and CDCA.