An improved synthesis of 6 alpha-ethylchenodeoxycholic acid (6ECDCA), a potent and selective agonist for the Farnesoid X Receptor (FXR)

作者：Yu Donna^*; Mattern Daniell L; Forman Barry M

来源：Steroids, 2012, 77(13): 1335-1338.

DOI：10.1016/j.steroids.2012.09.002

• Farnesoid X Receptor (FXR)
• Chenodeoxycholic acid (CDCA)
• 6 alpha-Ethylchenodeoxycholic acid (6ECDCA)
• Pyridinium chlorochromate (PCC)
• High-density lipoprotein (HDL)
• Stereoselective synthesis

The active, potent, and selective Farnesoid X Receptor (FXR) agonist 6 alpha-ethylchenodeoxycholic acid (6ECDCA) has been synthesized in improved yield compared to the published methodologies. The synthesis employed selective oxidation of one of the two hydroxyls of the readily-available starting material chenodeoxycholic acid (COCA) as a key step. After protection of the remaining hydroxyl, LDA/HMPA/Etl/PPTS provided an efficient deprotonation/ethylation/deprotection sequence. The two synthetic improvements that allow a productive yield are the use of PCC in the oxidation step, and the use of HMPA/ethyl iodide in the stereoselective alkylation step. This synthesis offers an economical and efficient strategy which provides a simple and cost-effective procedure for potential large-scale production of this promising FXR agonist, which is a research tool and potential drug substance of current interest.

• 出版日期2012-11