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

摘要

7 alpha-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, 7 alpha-hydroxy-cholest-4-en-3-one is the physiological substrate for cytochrome P450 8B1 (P450 881 or CYP8B1), the oxysterol 12 alpha-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 3desoxy-Delta(4)-7 alpha-formate steroid precursor to form 7 alpha-formyloxy-cholest-4-en-3-one, which was saponified to yield 7 alpha-hydroxy-cholest-4-en-3-one.