(3α,6α,7β,12α)-tetrahydroxy-5β-cholanic acid | 133269-41-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (3α,6α,7β,12α)-tetrahydroxy-5β-cholanic acid
• 英文别名: 3α,6α,7β,12α-tetrahydroxy-5β-cholanoic acid；12αOH-ω-muricholic acid；12αOH-ωMCA；omega MCA；3α,6α,7β,12α-tetrahydroxy-5β-cholan-24-oic acid；3alpha,6alpha,7beta,12alpha-Tetrahydroxy-5beta-cholan-24-oic Acid；(4R)-4-[(3R,5R,6R,7R,8R,9S,10R,12S,13R,14S,17R)-3,6,7,12-tetrahydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid
• CAS: 133269-41-7
• 化学式: C₂₄H₄₀O₆
• 分子量: 424.578
• InChiKey: COCMFMBNEAMQMA-FOKRCTQASA-N

物化性质

• 沸点：
  602.5±55.0 °C(Predicted)
• 密度：
  1.242±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  118
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  五氟苯酚 、 (3α,6α,7β,12α)-tetrahydroxy-5β-cholanic acid 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Urinary metabolomics in Fxr-null mice reveals activated adaptive metabolic pathways upon bile acid challenge

  摘要：

  Farnesoid X receptor (FXR) is a nuclear receptor that regulates genes involved in synthesis, metabolism, and transport of bile acids and thus plays a major role in maintaining bile acid homeostasis. In this study, metabolomic responses were investigated in urine of wild-type and Fxr-null mice fed cholic acid, an FXR ligand, using ultra-performance liquid chromatography (UPLC) coupled with electrospray time-of-flight mass spectrometry (TOFMS). Multivariate data analysis between wild-type and Fxr-null mice on a cholic acid diet revealed that the most increased ions were metabolites of p-cresol (4-methylphenol), corticosterone, and cholic acid in Fxr-null mice. The structural identities of the above metabolites were confirmed by chemical synthesis and by comparing retention time (RT) and/or tandem mass fragmentation patterns of the urinary metabolites with the authentic standards. Tauro-3 alpha,6,7 alpha,12 alpha-tetrol (3 alpha,6,7 alpha,12 alpha-tetrahydroxy-5 beta-cholestan-26-oyltaurine), one of the most increased metabolites in Fxr-null mice on a CA diet, is a marker for efficient hydroxylation of toxic bile acids possibly through induction of Cyp3a11. A cholestatic model induced by lithocholic acid revealed that enhanced expression of Cyp3a11 is the major defense mechanism to detoxify cholestatic bile acids in Fxr-null mice. These results will be useful for identification of biomarkers for cholestasis and for determination of adaptive molecular mechanisms in cholestasis.-Cho, J. Y., T. Matsubara, D. W. Kang, S. H. Ahn, K. W. Krausz, J. R. Idle, H. Luecke, and F. J. Gonzalez. Urinary metabolomics in Fxr-null mice reveals activated adaptive metabolic pathways upon bile acid challenge. J. Lipid Res. 2010. 51: 1063-1074.

  DOI：

  10.1194/jlr.m002923
• 作为产物：
  描述：

  3α,6α,12α-trihydroxy-7-oxo-5β-cholanoic acid 3,6-di-tert-butyldimethylsilyl ether 在 盐酸 、 氢氧化钾 、 2-甲基-2-丁醇 、 氢化钾 作用下， 以 甲醇 为溶剂， 反应 1.25h， 生成 (3α,6α,7β,12α)-tetrahydroxy-5β-cholanic acid
  参考文献：
  名称：

  潜在的胆汁酸代谢物。16.立体异构体3α，6，7，12α-四羟基-5β-胆酸的合成。

  摘要：

  四种可能的立体异构体3α，6,7,12α-四羟基-5β-胆酸（及其甲酯）的新合成路线，其中一种（3α，6α7β，12α）是新的，以及一些相关的化合物。另外，获得了新酸的5α-表位。获得高纯度的最终产物，用作人体生物样品中胆汁酸的分析参考化合物。简要讨论了通过质子和碳13核磁共振波谱对制备的立体异构体的分析结果，以及薄层和气液色谱特性。

  DOI：

  10.1016/0039-128x(90)90048-g

文献信息

• Polyhydroxylated bile acids for treatment of biliary disorders
  申请人：Qing Bile Therapeutics Inc.

  公开号：US10543220B2

  公开（公告）日：2020-01-28

  The invention provides, in part, polyhydroxylated bile acids for treating biliary disorders, for example, biliary disorders arising out of cholestasis of portal hypertension. The invention also provides, in part, polyhydroxylated bile acids for stimulating bile flow. New compounds 2α, 3α, 7α, 12α-tetrahydroxy-5β-cholanoic acid and 3α. 4α, 7α, 12α-tetrahydroxy-5β-cholanoic acid are disclosed, uses thereof and synthesis thereof.

  本发明部分提供了用于治疗胆道疾病的多羟基化胆汁酸，例如，门脉高压胆汁淤积引起的胆道疾病。本发明还部分提供了用于刺激胆汁流动的多羟基化胆汁酸。新化合物 2α，3α，7α，12α-四羟基-5β-胆酸和 3α。公开了 4α、7α、12α-四羟基-5β-胆酸及其用途和合成方法。
• Polyhydroxylated Bile Acids for Treatment of Biliary Disorders
  申请人：Wang Renxue

  公开号：US20110263546A1

  公开（公告）日：2011-10-27

  The invention provides, in part, polyhydroxylated bile acids for treating biliary disorders, for example, biliary disorders arising out of cholestasis or portal hypertension. The invention also provides, in part, polyhydroxylated bile acids for stimulating bile flow.
• POLYHYDROXYLATED BILE ACIDS FOR TREATMENT OF BILIARY DISORDERS
  申请人：LING VICTOR

  公开号：US20120277198A1

  公开（公告）日：2012-11-01

  The invention provides, in part, polyhydroxylated bile acids for treating biliary disorders, for example, biliary disorders arising out of cholestasis of portal hypertension. The invention also provides, in part, polyhydroxylated bile acids for stimulating bile flow. New compounds 2α,3α,7α,12α-tetrahydroxy-5β-cholanoic acid and 3α.4α,7α,12α-tetrahydroxy-5β-cholanoic acid are disclosed, uses thereof and synthesis thereof.
• US9295677B2
  申请人：——

  公开号：US9295677B2

  公开（公告）日：2016-03-29
• Urinary metabolomics in Fxr-null mice reveals activated adaptive metabolic pathways upon bile acid challenge
  作者：Joo-Youn Cho、Tsutomu Matsubara、Dong Wook Kang、Sung-Hoon Ahn、Kristopher W. Krausz、Jeffrey R. Idle、Hans Luecke、Frank J. Gonzalez

  DOI：10.1194/jlr.m002923

  日期：2010.5

  Farnesoid X receptor (FXR) is a nuclear receptor that regulates genes involved in synthesis, metabolism, and transport of bile acids and thus plays a major role in maintaining bile acid homeostasis. In this study, metabolomic responses were investigated in urine of wild-type and Fxr-null mice fed cholic acid, an FXR ligand, using ultra-performance liquid chromatography (UPLC) coupled with electrospray time-of-flight mass spectrometry (TOFMS). Multivariate data analysis between wild-type and Fxr-null mice on a cholic acid diet revealed that the most increased ions were metabolites of p-cresol (4-methylphenol), corticosterone, and cholic acid in Fxr-null mice. The structural identities of the above metabolites were confirmed by chemical synthesis and by comparing retention time (RT) and/or tandem mass fragmentation patterns of the urinary metabolites with the authentic standards. Tauro-3 alpha,6,7 alpha,12 alpha-tetrol (3 alpha,6,7 alpha,12 alpha-tetrahydroxy-5 beta-cholestan-26-oyltaurine), one of the most increased metabolites in Fxr-null mice on a CA diet, is a marker for efficient hydroxylation of toxic bile acids possibly through induction of Cyp3a11. A cholestatic model induced by lithocholic acid revealed that enhanced expression of Cyp3a11 is the major defense mechanism to detoxify cholestatic bile acids in Fxr-null mice. These results will be useful for identification of biomarkers for cholestasis and for determination of adaptive molecular mechanisms in cholestasis.-Cho, J. Y., T. Matsubara, D. W. Kang, S. H. Ahn, K. W. Krausz, J. R. Idle, H. Luecke, and F. J. Gonzalez. Urinary metabolomics in Fxr-null mice reveals activated adaptive metabolic pathways upon bile acid challenge. J. Lipid Res. 2010. 51: 1063-1074.