1448-36-8Relevant articles and documents
Molecular association via halogen bonding and other weak interactions in the crystal structures of 11-bromo-12-oxo-5β-cholan derivatives
Salunke, Deepak B.,Hazra, Braja G.,Gonnade, Rajesh G.,Pore, Vandana S.,Bhadbhade, Mohan M.
, p. 246 - 253 (2008)
Methyl 3α,7α-diacetoxy-12-oxo-5β-cholan-24-oate 2, methyl 11α-bromo-3α,7α-diacetoxy-12-oxo-5β-cholan-24-oate 3, methyl 11β-bromo-3α,7α-diacetoxy-12-oxo-5β-cholan-24-oate 4 and methyl 11,11-dibromo-3α,7α-diacetoxy-12-oxo-5β-cholan-24-oate 5 were synthesized. The crystal structures of these molecules were resolved to study the effect of bulky bromine atom in the steroid skeleton of cholic acid with different stereo-chemical orientations at C-11 on the two-dimensional arrangement of molecules and solid-state properties. All the molecules associate only via weak intermolecular interactions in their crystal structures, notable one being the Halogen Bonded assembly (C-Br...O) in 5.
Chemical Synthesis of Rare Natural Bile Acids: 11α-Hydroxy Derivatives of Lithocholic and Chenodeoxycholic Acids
Namegawa, Kazunari,Iida, Kyoko,Omura, Kaoru,Ogawa, Shoujiro,Hofmann, Alan F.,Iida, Takashi
, p. 403 - 411 (2018)
A method for the preparation of 11α-hydroxy derivatives of lithocholic and chenodeoxycholic acids, recently discovered to be natural bile acids, is described. The principal reactions involved were (1) elimination of the 12α-mesyloxy group of the methyl esters of 3α-acetate-12α-mesylate and 3α,7α-diacetate-12α-mesylate derivatives of deoxycholic acid and cholic acid with potassium acetate/hexamethylphosphoramide; (2) simultaneous reduction/hydrolysis of the resulting △11-3α-acetoxy and △11-3α,7α-diacetoxy methyl esters with lithium aluminum hydride; (3) stereoselective 11α-hydroxylation of the △11-3α,24-diol and △11-3α,7α,24-triol intermediates with B2H6/tetrahydrofuran (THF); and (4) selective oxidation at C-24 of the resulting 3α,11α,24-triol and 3α,7α,11α,24-tetrol to the corresponding C-24 carboxylic acids with NaClO2 catalyzed by 2,2,6,6-tetramethylpiperidine 1-oxyl free radical (TEMPO) and NaClO. In summary, 3α,11α-dihydroxy-5β-cholan-24-oic acid and 3α,7α,11α-trihydroxy-5β-cholan-24-oic acid have been synthesized and their nuclear magnetic resonance (NMR) spectra characterized. These compounds are now available as reference standards to be used in biliary bile acid analysis.
Cyclocholates with 12-Oxo and 7,12-Oxo Groups
Gao, Hongwu,Dias, Jerry Ray
, p. 719 - 724 (1998)
Syntheses of bile acid cyclooligomers with 12- and 7,12-oxo groups (6a-d, 7a-c, 8a-b) by the Yamaguchi method are described. Cyclotrimerization is the principal reaction route for these cholic acid systems. Conversion of 7- and 12-hydroxy groups in cholic acid (la-b) to oxo groups (4a-c, 5a-c), followed by macrocyclization (6a-d, 7a-c, 8a-b) and selective reduction of the oxo groups back to hydroxy ones without cleaving the 24-carboxylic ester linkages (11) constitutes a new strategy in the synthesis of cyclocholates having unprotected hydroxy groups.
Ring-closing metathesis towards functionalised pentacyclic steroids
Ibrahim-Ouali, Malika,Bouleghlem, Hocine,Aouf, Nour-Eddine
, p. 1859 - 1862 (2012)
A new synthetic pathway towards pentacyclic steroids was described via a ring-closing metathesis reaction as the key step.
Synthesis of heterosteroids. First synthesis of oxa steroid from cholic acid
Ibrahim-Ouali, Malika,Botsi-Nkomendi, Nicaise,Rocheblave, Luc
, p. 93 - 95 (2010)
We wish to report here a new and efficient partial synthesis of 3-oxa-5β-steroid, the first oxa steroid synthesized from cholic acid.
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Malik,A.A.,Sharts,C.M.
, p. 395 (1987)
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Novel liver-specific nitric oxide (NO) releasing drugs with bile acid as both NO carrier and targeting ligand
Jin, Xue-Yuan,Fan, Shi-Yong,Li, Hong-Wu,Shi, Wei-Guo,Chen, Wei,Wang, Hui-Fen,Zhong, Bo-Hua
, p. 787 - 790 (2014)
Novel liver-specific nitric oxide (NO) releasing drugs with bile acid as both the NO carrier and targeting ligand were designed and synthesized by direct nitration of the hydroxyl group in bile acids or the 3-O-hydroxyl alkyl derivatives, with the intact 24-COOH being preserved for hepatocyte specific recognition. Preliminary biological evaluation revealed that oral administrated targeted conjugates could protect mice against acute liver damage induced by acetaminophen or carbon tetrachloride. The nitrate level in the liver significantly increased after oral administration of 1e while nitrate level in the blood did not significantly change. Co-administration of ursodeoxycholic acid (UDCA) significantly antagonized the increase of nitrate in the liver resulted by administration of 1e.
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Kuwada,Morimoto
, p. 147,150 (1942)
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Synthesis and micellar mimic properties of bile acid trimers
Lu, Jinrong,Liu, Chulong,Hu, Jun,Ju, Yong
, p. 1302 - 1305 (2013)
Two fan-shaped bile acid trimers have been synthesized via Cu I-catalyzed azide-alkyne cycloaddition (CuAAC) 'click chemistry', and their extraction experiments of cresol red sodium (CR) and pyrene were investigated in the polar and non-polar solvents, respectively. The transmission electron microscopy (TEM) results showed that the homogenous hollow capsules formed with the diameter size range of 40-70 nm in a solution of water and acetone. Thus the amphiphilicity of fan-shaped bile acid trimers might be used as the promising candidate in biological and drug delivery applications.
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Bergmann,Pace
, p. 477 (1943)
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Discovery of novel cholic acid derivatives as highly potent agonists for G protein-coupled bile acid receptor
Chen, Xin,Hou, Wenwen,Lu, Xin,Luo, Zhijie,Qian, Mingcheng,Sun, Jingjing,Wu, Yi,Xue, Caile,Zhang, Qianxi,Zhao, Shuai
, (2022/01/03)
In this study, fourteen new cholic acid (CA) derivatives were designed and synthesized, and the GloSensor cAMP accumulation assay indicated that all derivatives could activate the Takeda G protein-coupled receptor 5 (TGR5). Methylation of 7- and 12-hydroxyl groups in CA significantly increased TGR5 agonism for the new derivatives. For example, 7,12-dimethoxy derivative B1 exhibited 78-fold higher potency for TGR5 than the 7,12-dihydroxyl derivative A1 and 258-fold higher potency than CA itself. On the other hand, A1 positively modulated chenodeoxycholic acid (CDCA) functional activity in TGR5, whereas B1 did not show similar activity. Molecular docking experiments indicated that A1 formed a hydrogen bond between the 12-OH and amino acid Thr131 of TGR5, which is significant for its allosteric property. However, methylation at the 12-hydroxyl group in CA (derivative B1) disrupted this pivotal H-bond. Therefore, the free 12-hydroxyl group is essential for the CA derivatives in TGR5 allosteric agonism. Overall, we discovered a highly potent TGR5 agonist, B1, which can be used as lead compound for further study.
G protein coupled cholic acid receptor endogenous ligand derivatives and preparation method and application thereof in anti-tumor activity
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Paragraph 0014; 0024; 0083-0086, (2021/05/29)
The invention belongs to the field of medicinal chemistry, and particularly discloses G protein coupled cholic acid receptor endogenous ligand derivatives and a preparation method and application thereof in anti-tumor activity. Different cholic acid parent structures are used as raw materials, esterification reaction is carried out under the action of a catalyst, methylation is carried out after protection by a protecting group, and a series of novel cholic acid series derivatives are finally obtained through deprotection, hydrolysis reaction and amide coupling reaction. An MTT colorimetric method is used for carrying out anti-cancer activity test on the synthesized new derivatives, and the results show that the series of synthesized G protein coupled cholic acid receptor endogenous ligand derivatives have better anticancer activity.
Engineering Regioselectivity of a P450 Monooxygenase Enables the Synthesis of Ursodeoxycholic Acid via 7β-Hydroxylation of Lithocholic Acid
Grobe, Sascha,Badenhorst, Christoffel P. S.,Bayer, Thomas,Hamnevik, Emil,Wu, Shuke,Grathwol, Christoph W.,Link, Andreas,Koban, Sven,Brundiek, Henrike,Gro?johann, Beatrice,Bornscheuer, Uwe T.
supporting information, p. 753 - 757 (2020/12/01)
We engineered the cytochrome P450 monooxygenase CYP107D1 (OleP) from Streptomyces antibioticus for the stereo- and regioselective 7β-hydroxylation of lithocholic acid (LCA) to yield ursodeoxycholic acid (UDCA). OleP was previously shown to hydroxylate testosterone at the 7β-position but LCA is exclusively hydroxylated at the 6β-position, forming murideoxycholic acid (MDCA). Structural and 3DM analysis, and molecular docking were used to identify amino acid residues F84, S240, and V291 as specificity-determining residues. Alanine scanning identified S240A as a UDCA-producing variant. A synthetic “small but smart” library based on these positions was screened using a colorimetric assay for UDCA. We identified a nearly perfectly regio- and stereoselective triple mutant (F84Q/S240A/V291G) that produces 10-fold higher levels of UDCA than the S240A variant. This biocatalyst opens up new possibilities for the environmentally friendly synthesis of UDCA from the biological waste product LCA.
