Chemical synthesis of 7α-hydroxycholest-4-en-3-one, a biomarker for irritable bowel syndrome and bile acid malabsorption

  • Steroids. 2019 Nov;151:108449. doi: 10.1016/j.steroids.2019.108449.
Samuel D Offei  1 ,  Hadi D Arman  1 ,  Francis K Yoshimoto  2
Affiliations
  • 1. Department of Chemistry, The University of Texas at San Antonio, San Antonio, TX 78249-0698, United States.
  • 2. Department of Chemistry, The University of Texas at San Antonio, San Antonio, TX 78249-0698, United States. Electronic address: [email protected].
PMID: 31302111 DOI: 10.1016/j.steroids.2019.108449
Abstract

7α-Hydroxy-cholest-4-en-3-one is a biomarker for bile acid loss, irritable bowel syndrome, and Other Diseases associated with defective bile acid biosynthesis. Furthermore, 7α-hydroxy-cholest-4-en-3-one is the physiological substrate for Cytochrome P450 8B1 (P450 8B1 or CYP8B1), the oxysterol 12α-hydroxylase enzyme implicated in obesity and cardiovascular health. We report the chemical synthesis of this physiologically important oxysterol beginning with Cholesterol. The key feature of this synthesis involves a regioselective C3-allylic oxidation of a 3-desoxy-Δ4-7α-formate steroid precursor to form 7α-formyloxy-cholest-4-en-3-one, which was saponified to yield 7α-hydroxy-cholest-4-en-3-one.

Keywords
Cytochrome P450; Irritable bowel syndrome; Oxysterols; Regioselective oxidation; Steroids.
Products