title: An improved synthesis of 6α-ethylchenodeoxycholic acid (6ECDCA), a potent and selective agonist for the Farnesoid X Receptor (FXR).
abstract: The active, potent, and selective Farnesoid X Receptor (FXR) agonist 6α-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 (CDCA) as a key step. After protection of the remaining hydroxyl, LDA/HMPA/EtI/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.
authors.affiliation: Department of Diabetes, Endocrinology and Metabolism, The Beckman Research Institute at The City of Hope National Medical Center, Duarte, CA 91010, USA. dyu@coh.org
authors.forename: Donna
authors.initials: D
authors.lastname: Yu
authors.forename: Daniell L
authors.initials: DL
authors.lastname: Mattern
authors.forename: Barry M
authors.initials: BM
authors.lastname: Forman
mesh_terms: D000818:Animals; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D013379:Substrate Specificity; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D002635:Chenodeoxycholic Acid; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C464660:obeticholic acid