An improved synthesis of 6α-ethylchenodeoxycholic acid (6ECDCA), a potent and selective agonist for the Farnesoid X Receptor (FXR)
| Autor: | Barry M. Forman, Daniell L. Mattern, Donna Yu |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Pharmacology
Agonist Stereochemistry medicine.drug_class Organic Chemistry Clinical Biochemistry Ethyl iodide Receptors Cytoplasmic and Nuclear Chemistry Techniques Synthetic Alkylation Chenodeoxycholic Acid Biochemistry Substrate Specificity chemistry.chemical_compound Endocrinology Deprotonation chemistry Chenodeoxycholic acid Yield (chemistry) medicine Animals Stereoselectivity Farnesoid X receptor Molecular Biology |
| Zdroj: | Steroids. 77:1335-1338 |
| ISSN: | 0039-128X |
| DOI: | 10.1016/j.steroids.2012.09.002 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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