10538-55-3Relevant articles and documents
p-Toluenesulfonic acid/methanol: mild reagent for the preparation of bile acid methyl esters.
Dayal,Speck,Bagan,Tint,Salen
, p. 239 - 242 (1981)
An improved method for the preparation of bile acid methyl esters is described. This is achieved by the addition of catalytic amounts of p-toluenesulfonic acid in a solution of bile acid in methanol. Advantages of this procedure over conventional methods include (1) use of a mild solid acid catalyst which prevents the formation of undesirable byproducts, (2) isolation of a solid product of high purity and (3) utilization of a relatively safe reagent in comparison to other methods involving diazomethane, hydrochloric acid or sulfuric acid.
Fluorous-tag assisted synthesis of bile acid-bisphosphonate conjugates: Via orthogonal click reactions: An access to potential anti-resorption bone drugs
Massarenti, Chiara,Bortolini, Olga,Fantin, Giancarlo,Cristofaro, Dario,Ragno, Daniele,Perrone, Daniela,Marchesi, Elena,Toniolo, Gianluca,Massi, Alessandro
, p. 4907 - 4920 (2017)
The synthesis of a small collection of novel bile acid-bisphosphonate (BA-BP) conjugates as potential drug candidates is reported. The disclosed methodology relied on the installation of azide and thiol functionalities at the head and tail positions, respectively, of the BA scaffold and its subsequent decoration by orthogonal click reactions (copper-catalyzed azide-alkyne cycloaddition, thiol-ene or thiol-yne coupling) to introduce BP units and a fluorophore. Because of the troublesome isolation of the target conjugates by standard procedures, the methodology culminated with the functionalization of the BA scaffold with a light fluorous tag to rapidly and efficiently purify intermediates and final products by fluorous solid-phase extraction.
Synthesis and characterization of organometallic rhenium(I{cyrillic, ukrainian}) and technetium(I{cyrillic, ukrainian}) bile acid complexes
Huang, Liliang,Zhu, Hua,Xu, Xiaoping,Zhang, Chunchun,Shen, Yu-Mei
, p. 3247 - 3253 (2009)
Eight bile acid derivatives have been synthesized with alkyl chains of various length based tridentate ligand chelating system. These derivatives have been reacted with the precursor [Et4N]2[Re(CO)3Br3] and fac-[M(CO)3(H2O)3]+ (M = 99mTc, Re) in ethanol or ethanol-aqueous media to form water-soluble and stable organometallic complexes in good yields. 1H NMR, 13C NMR, IR and elemental analysis or HRMS spectroscopic analyses confirmed the tridentate complexation of the metal-tricarbonyl fragment exclusively via the tridentate chelates. In addition, the corresponding radioactive technetium-99m complexes were prepared successfully and challenged for stability in physiological phosphate buffer at 37 °C for 24 h. No decomposition of the complexes could be detected under the condition proving the stability of these complexes.
Synthesis and antimicrobial evaluation of bile acid tridentate conjugates
Huang, Liliang,Sun, Yanhong,Zhu, Hua,Zhang, Yuanqing,Xu, Jia,Shen, Yu-Mei
, p. 701 - 706 (2009)
Two series of novel bile acid tridentate conjugates with different linkers were synthesized and characterized, and their biological activities in vitro were evaluated. The procedure was straightforward and efficient to be carried out with high overall yield. The antimicrobial activity of the synthesized compounds against Saccharomyces cerevisiae, Aspergillus niger, Escherichia coli and Staphylococcus aureus was investigated in vitro. The best activity of minimal inhibitory concentrations (MICs) for 1c, 1c′, 2c and 2c′ against S. cerevisiae was up to 0.125 μg/mL.
Microwave-induced organic reactions of bile acids: Esterification, deformylation and deacetylation using mild reagents
Dayal, B.,Rao, Keshava,Salen, G.
, p. 453 - 457 (1995)
An efficient and convenient procedure for the esterification, deformylation, and deacetylation of bile acids is described.This is achieved by the addition of a catalytic amount of methanesulfonic acid or para-toluene sulfonic acid to a solution of bile acid in methanol in the domestic microwave oven.All these reactions were completed in the microwave oven within 1-3 min at 60percent power (390 W) and the desired bile acids, namely trihydroxy-5β-cholestanoic acid, (23R)-3α,7α,23-trihydroxy-5β-cholan-24-oic acid, ursocholic acid and 7-ketolithocholic acid were isolated in 86-94percent yield. - Keywords: microwave; bile acids; esterification; deformylation; deacetylation; methanesulfonic acid/methanol; para-toluene sulfonic acid/methanol
UGT-dependent regioselective glucuronidation of ursodeoxycholic acid and obeticholic acid and selective transport of the consequent acyl glucuronides by OATP1B1 and 1B3
Zhou, Dandan,Kong, Linghua,Jiang, Yiguo,Wang, Cheng,Ni, Yao,Wang, Yedong,Zhang, Hongjian,Ruan, Jianqing
, (2019)
Ursodeoxycholic acid (UDCA) is a major effective constituent of bear bile powder, which is widely used as function food in China and is documented in the Chinese pharmacopoeia as a traditional Chinese medicine. UDCA has been developed as the only accepted therapy by the US FDA for primary biliary cholangitis. Recently, the US FDA granted accelerated approval to obeticholic acid (OCA), a semisynthetic bile acid derivative from chenodeoxycholic acid, for primary biliary cholangitis. However, some perplexing toxicities of UDCA have been reported in the clinic. The present work aimed to investigate the difference between UDCA and OCA in regard to potential metabolic activation through acyl glucuronidation and hepatic accumulation of consequent acyl glucuronides. Our results demonstrated that the metabolic fates of UDCA and OCA were similar. Both UDCA and OCA were predominantly metabolically activated by conjugation to the acyl glucuronide in human liver microsomes. UGT1A3 played a predominant role in the carboxyl glucuronidation of both UDCA and OCA, while UGT2B7 played a major role in their hydroxyl glucuronidation. Further uptake studies revealed that OATP1B1- and 1B3-transfected cells could selectively uptake UDCA acyl glucuronide, but not UDCA, OCA, and OCA acyl glucuronide. In summary, the liver disposition of OCA is different from that of UDCA due to hepatic uptake, and liver accumulation of UDCA acyl glucuronide might be related to the perplexing toxicities of UDCA.
Chemical synthesis of 3β-sulfooxy-7β-hydroxy-24-nor-5-cholenoic acid: An internal standard for mass spectrometric analysis of the abnormal Δ5-bile acids occurring in Niemann-Pick disease
Kakiyama, Genta,Muto, Akina,Shimada, Miki,Mano, Nariyasu,Goto, Junichi,Hofmann, Alan F.,Iida, Takashi
, p. 766 - 772 (2009)
In Niemann-Pick disease, type C1, increased amounts of 3β,7β-dihydroxy-5-cholenoic acid are reported to be present in urinary bile acids. The compound occurs as a tri-conjugate, sulfated at C-3, N-acetylglucosamidated at C-7, and N-acylamidated with taurine or glycine at C-24. For sensitive LC-MS/MS analysis of this bile acid, a suitable internal standard is needed. We report here the synthesis of a satisfactory internal standard, 3β-sulfooxy-7β-hydroxy-24-nor-5-cholenoic acid (as the disodium salt). The key reactions involved were (1) the so-called "second order" Beckmann rearrangement (one-carbon degradation at C-24) of hyodeoxycholic acid (HDCA) 3,6-diformate with sodium nitrite in a mixture of trifluoroacetic anhydride and trifluoroacetic acid, (2) simultaneous inversion at C-3 and elimination at C-6 of the ditosylate derivatives of the resulting 3α,6α-dihydroxy-24-nor-5β-cholanoic acid with potassium acetate in aqueous N,N-dimethylformamide, and (3) regioselective sulfation at C-3 of an intermediary 3β,7β-dihydroxy-24-nor-Δ5 derivative using sulfur trioxide-trimethylamine complex. Overall yield of the desired compound was 1.8% in 12 steps from HDCA.
Structural analysis and antitussive evaluation of five novel esters of verticinone and bile acids
Zhang, Jiu-liang,Wang, Hui,Pi, Hui-fang,Ruan, Han-li,Zhang, Peng,Wu, Ji-zhou
, p. 424 - 434 (2009)
Shedan-Chuanbei powder, a complex of traditional Chinese medicine preparation, which consists of Snake Bile (Chinese name "Shedan") and Fritillariae Cirrhosae (Chinese name "Chuanbei"), is the most popular antitussive and expectorant formulation in Chinese communities. However, the clinical application of Shedan-Chuanbei powder is now stringently limited because of the shortage of the two crude medicinal materials, especially for the sake of animal protection. In addition, the inherent defects of the most of the complex of traditional Chinese medicine such as the indistinct basal pharmacodynamic materials and the difficulties in quality control had blocked them heading into the international medicinal market. So we attempted to seek new substitute for Shedan-Chuanbei powder for antitussive drugs. In order to gain some new compounds with better bioactivity and attenuated toxicity, we tried to combine two kinds of drugs through ester bond. Enlightened with "combination principle" in drug discovery, we synthesized five novel esters of verticinone and bile acids, both of which are the major bioactive components in Shedan-Chuanbei powder. We then evaluated the antitussive activity and the acute toxicity of the five ester-linked compounds. The five ester-linked compounds had much more potent antitussive activity and expectorant activity than single bile acids at the same doses, and had equivalent antitussive activity and expectorant activity in comparison with about double moles dose of the monomer verticinone. Especially, cholic acid-verticinone ester had much more potent antitussive effects than the monomer verticinone or cholic acid at the same dose. A further acute toxicity study showed that the LD50 values of the five ester-linked compounds exceeded 3.5 g/kg by intraperitoneal injection in mice. Based on the studies of pharmacology and acute toxicity, the five ester-linked compounds have synergic pharmacodynamic action and attenuated toxicity compared with single verticinone and single bile acids.
Synthesis and Biological Evaluation of Bile Acid Analogues Inhibitory to Clostridium difficile Spore Germination
Stoltz, Kristen L.,Erickson, Raymond,Staley, Christopher,Weingarden, Alexa R.,Romens, Erin,Steer, Clifford J.,Khoruts, Alexander,Sadowsky, Michael J.,Dosa, Peter I.
, p. 3451 - 3471 (2017)
Standard antibiotic-based strategies for the treatment of Clostridium difficile infections disrupt indigenous microbiota and commonly fail to eradicate bacterial spores, two key factors that allow recurrence of infection. As an alternative approach to controlling C. difficile infection, a series of bile acid derivatives have been prepared that inhibit taurocholate-induced spore germination. These analogues have been evaluated in a highly virulent NAP1 strain using optical density and phase-contrast microscopy assays. Heterocycle substitutions at C24 were well-tolerated and several tetrazole-containing derivatives were highly potent inhibitors in both assays, with complete inhibition of spore germination observed at 10-25 μM. To limit intestinal absorption, C7-sulfated analogues designed to avoid active and passive transport pathways were prepared. One of these derivatives, compound 21b, was found to be a potent inhibitor of C. difficile spore germination and poorly permeable in a Caco-2 model of intestinal epithelial absorption, suggesting that it is likely to be gut-restricted.
SYNTHETIC DERIVATIVES OF CHOLIC ACID 7-SULFATE AND USES THEREOF
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Paragraph 00365-00366, (2020/07/05)
The compositions and methods provided herein are related, in part, to the discovery of cholic acid 7-sulfate as a treatment for diabetes. Provided herein is a method for treating a metabolic disorder (e.g., diabetes, obesity), or an inflammatory disease (e.g., Crohn's disease, inflammatory bowel disease, ulcerative colitis, pancreatitis, hepatitis, appendicitis, gastritis, diverticulitis, celiac disease, food intolerance, enteritis, ulcer, gastroesophageal reflux disease (GERD), psoriatic arthritis, psoriasis, and rheumatoid arthritis) in a subject in need thereof comprising administering to a subject a compound of Formulae (I)-(XVII).
