4651-67-6Relevant articles and documents
Ido,Sakurai
, p. 51,53 (1939)
An expedient synthesis of 6α-fluoroursodeoxycholic acid
Koenigsberger, Kurt,Chen, Guang-Pei,Vivelo, James,Lee, George,Fitt, John,McKenna, Joseph,Jenson, Todd,Prasad, Kapa,Repic, Oljan
, p. 665 - 669 (2002)
Optimization of the synthesis of 6α-fluoroursodeoxycholic acid 1 is described starting from the commercially available 2. The penultimate intermediate 16 was made in eight synthetic steps but in only four operations in an overall yield of 57%. The highlights are flourination of hydroxyketo acid 11 using Selectfluor through the intermediacy of silyl enol ether 12, conversion of 13 to 14 via equilibration of fluoroketone, esterification, and acylation. The drug substance 1 was prepared from mesylate 16 using potassium superoxide followed by a mild reductive workup using methoxydiethylborane.
(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.
A method of synthesis of ursodesoxycholic acid(UDCA) using bile salt hydrolase(BSH) from Porcine intestinal flora Bifidobacterium thermophilum
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Paragraph 0045-0046, (2020/07/11)
The present invention relates to a method for synthesizing ursodesoxycholic acid (UDCA) from porcine bile acid by using bile salt hydrolase (BSH) derived from Bifidobacterium thermophilum in porcine gut microbiota. The present inventors have found that, compared to existing synthesis methods involving repeated purification processes, an UDCA synthesis method using the BSH of Bifidobacterium thermophilum in porcine gut microbiota is simple and time-saving; provides remarkable advantages in terms of high-throughput production and stability; is significantly more economical; and can increase an UDCA yield. In addition, the present invention is expected to provide a significant economic advantage in that it provides high-value added UDCA effective in improving hepatic functions, alleviating fatigue through liver improvement, cholesterol reduction, gallstone dissolution, primary biliary cirrhosis, and the like by utilizing porcine waste by-products.(AA) First step : Extract bile acid derived from by-products(BB) Second step : Extract BSH enzyme(CC) Third step : Extract CDCA(DD) Fourth step : Synthesize and purify UDCA(EE) Fifth step : Analyze UDCA(FF) Process of extracting bile acid for use in UDCA synthesis in by-products, Extract bile acid soluble by use of organic solvent methanol and evaporate methanol to obtain bile acid(GG) Extract BSH enzyme by expression and purification of BSH from lactic acid bacteria having BSH enzyme used in CDCA extraction(HH) Extract bile acid from CDCA as a measure to increase the purity and yield of UDCA from extracted bile acid(II) Synthesize UDCA by redox reaction using CDCA from the bile acid extracted from respective by-products(JJ) Analyze CLA via HPLC in order to confirm the synthesis and yield of synthesized UDCACOPYRIGHT KIPO 2020
