10538-59-7Relevant articles and documents
Facial synthesis of key intermediate of obeticholic acid via Pd-catalyzed Kumada-Tamao-Corriu cross-coupling reaction
Di, Xiangjie,Han, Jie,Huang, Qingfei,Wang, Qiwei,Wang, Yuanhua,Wei, Xia,Zhong, Liu,Zhu, Jin,Zou, Sheng
, (2020)
Obeticholic acid (OCA) is used to treatment for Primary Biliary Cholangitis and other Famesoid X Receptor related diseases. Through the palladium catalyzed Kumada-Tamao-Corriu cross-coupling reaction, a novel and efficient method for synthesis of OCA with satisfied yield was successfully developed. The absolute configuration of the key intermediate was confirmed by Single-crystal X-ray Diffraction. It affords good strategy for large-scale synthesis of OCA.
BILE ACIDS LXIX. SELECTIVE K-SELECTRIDE REDUCTION OF 3,7-DIKETO STEROIDS
Tal, Daniel M.,Frisch, G. Douglas,Elliott, William H.
, p. 851 - 854 (1984)
The K-Selectride reduction at low temperature (-45 C) of 7-oxo-5α-cholestan-3β-yl acetate and methyl 7-oxo-3α-hydroxy-5β-cholanoate resulted in almost quantitative yield of the 7α-alcohol in the 5α-compound but only moderate yield of the 5β-analog.The simultaneous reduction of two carbonyl in the 3 and 7 positions afforded good to excellent yields of the diaxial diol in planar steroids (methyl 3,7-dioxo-5α-cholanoate, 3,7-dioxo-5α-cholestane and methyl 3,7-dioxo-5α-cholestan-27-oate) and only 14percent of 3α,7α-(OH)2 from methyl 3,7-dioxo-5β-cholanoate.
(E)-7-Ethylidene-lithocholic Acid (7-ELCA) Is a Potent Dual Farnesoid X Receptor (FXR) Antagonist and GPBAR1 Agonist Inhibiting FXR-Induced Gene Expression in Hepatocytes and Stimulating Glucagon-like Peptide-1 Secretion From Enteroendocrine Cells
Dracinsky, Martin,Drastik, Martin,Kaspar, Miroslav,Klepetarova, Blanka,Kronenberger, Thales,Kudova, Eva,Micuda, Stanislav,Pavek, Petr,Stefela, Alzbeta
, (2021/09/08)
Bile acids (BAs) are key signaling steroidal molecules that regulate glucose, lipid, and energy homeostasis via interactions with the farnesoid X receptor (FXR) and G-protein bile acid receptor 1 (GPBAR1). Extensive medicinal chemistry modifications of the BA scaffold led to the discovery of potent selective or dual FXR and GPBAR1 agonists. Herein, we discovered 7-ethylidene-lithocholic acid (7-ELCA) as a novel combined FXR antagonist/GPBAR1 agonist (IC50 = 15?μM/EC50 = 26?nM) with no off-target activation in a library of 7-alkyl substituted derivatives of BAs. 7-ELCA significantly suppressed the effect of the FXR agonist obeticholic acid in BSEP and SHP regulation in human hepatocytes. Importantly, 7-ELCA significantly stimulated the production of glucagon-like peptide-1 (GLP-1), an incretin with insulinotropic effect in postprandial glucose utilization, in intestinal enteroendocrine cells. We can suggest that 7-ELCA may be a prospective approach to the treatment of type II diabetes as the dual modulation of GPBAR1 and FXR has been supposed to be effective in the synergistic regulation of glucose homeostasis in the intestine.
