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

Steroids. 2020 May:157:108594. doi: 10.1016/j.steroids.2020.108594. Epub 2020 Feb 15.

Abstract

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.

Keywords: Chenodeoxycholic acid; Cholic acid; Hydrogen inversion; Hyodeoxycholic acid; Selective oxidation; ω-Muricholic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cholic Acid / chemical synthesis*
  • Cholic Acid / chemistry
  • Deoxycholic Acid / chemistry*
  • Molecular Conformation
  • Stereoisomerism

Substances

  • Deoxycholic Acid
  • hyodeoxycholic acid
  • Cholic Acid