(3alpha,5beta,6beta,7alpha,12alpha)-3,6,7,12-四羟基胆烷-24-酸 | 80875-93-0

• 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
• 中文名称: (3alpha,5beta,6beta,7alpha,12alpha)-3,6,7,12-四羟基胆烷-24-酸
• 中文别名: 胆烷-24-酸,3,6,7,12-四羟基-,(3a,5b,6b,7a,12a)-
• 英文名称: 3α,6β,7α,12α-tetrahydroxy-5β-cholan-24-oic acid
• 英文别名: 3alpha,6beta,7alpha,12alpha-Tetrahydroxy-5beta-cholan-24-oic Acid；(4R)-4-[(3R,5R,6S,7S,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: 80875-93-0
• 化学式: C₂₄H₄₀O₆
• 分子量: 424.578
• InChiKey: COCMFMBNEAMQMA-VGKGADPCSA-N

物化性质

• 物理描述：
  Solid
• 熔点：
  165-167°C

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：

  甲醇 、 (3alpha,5beta,6beta,7alpha,12alpha)-3,6,7,12-四羟基胆烷-24-酸 在 对甲苯磺酸 作用下， 以100%的产率得到methyl 3α,6β,7α,12α-tetrahydroxy-5β-cholanoate
  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
• 作为产物：
  描述：

  胆酸 在 4-二甲氨基吡啶 、 对甲苯磺酸 吡啶 、 N-溴代丁二酰亚胺(NBS) 、 zinc(II) tetrahydroborate 、 2,6-二叔丁基-4-甲基苯酚 、 三氟化硼乙醚 、 溴 、 溶剂黄146 、 间氯过氧苯甲酸 、 potassium hydroxide 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 苯 为溶剂， 反应 181.0h， 生成 (3alpha,5beta,6beta,7alpha,12alpha)-3,6,7,12-四羟基胆烷-24-酸
  参考文献：
  名称：

  [EN] POLYHYDROXYLATED BILE ACIDS FOR TREATMENT OF BILIARY DISORDERS
  [FR] ACIDES BILIAIRES POLYHYDROXYLÉS POUR LE TRAITEMENT DES TROUBLES BILIAIRES

  摘要：

  公开号：

  WO2011022838A8

文献信息

• Synthesis of 6-hydroxylated bile acids and identification of 3.ALPHA.,6.ALPHA.,7.ALPHA.,12.ALPHA.-tetrahydroxy-5.BETA.-cholan-24-oic acid in human meconium and neonatal urine.
  作者：Takao KUROSAWA、Reijiro MAHARA、Hiroshi NITTONO、Masahiko TOHMA

  DOI：10.1248/cpb.37.557

  日期：——

  Three 6-hydroxylated bile acids, 3α, 6α, 7α, 12α-, 3α, 6β, 7α, 12α- and 3α, 6β, 7β, 12α-tetrahydroxy-5β-cholan-24-oic acids, were synthesized from methyl cholate, and a sensitive method was developed for analyzing them by gas chromatography-mass spectrometry for the stoichiometric study of fetal bile acids. 3α, 6α, 7α, 12α-Tetrahydroxy-5β-cholan-24-oic acid (6α-hydroxylated cholic acid) was identified from human meconium and healthy neonatal urine by comparison with the mass spectrum of the reference compound. In human meconium, 6α-hydroxylated cholic and chenodeoxycholic acids were determined in 1.2% and 29.0% of the total bile acids, respectively. We discuss the significance of hydroxylation at the C-1β and C-6α positions of bile acids and their elimination in fetal and neonatal periods.

  从胆酸甲酯合成了三种 6-羟基化胆汁酸，3α、6α、7α、12α-、3α、6β、7α、12α- 和 3α、6β、7β、12α-四羟基-5β-cholan-24-oic 酸，并开发了一种灵敏的方法，通过气相色谱-质谱法对其进行分析，以进行胎儿胆汁酸的化学计量研究。通过与参考化合物的质谱比较，从人胎便和健康新生儿尿液中鉴定出 3α、6α、7α、12α-四羟基-5β-胆烷-24-oic 酸（6α-羟基化胆酸）。在人胎便中，6α-羟基化胆酸和鹅去氧胆酸分别占总胆汁酸的 1.2% 和 29.0%。我们讨论胆汁酸 C-1β 和 C-6α 位置羟基化的重要性及其在胎儿和新生儿时期的消除。
• 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。
• 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.
• Identification of 3,6,7,12-tetrahydroxy-5β-cholan-24-oic acids in human biologic fluids
  作者：Michiko Yoshii、Kenji Kihira、Junichi Shoda、Toshiaki Osuga、Takahiko Hoshita

  DOI：10.1016/0039-128x(90)90090-x

  日期：1990.11

  Unusual bile acids, 3-alpha, 6-alpha, 7-alpha, 12-alpha-,3-alpha, 6-beta, 7-alpha, 12-alpha-, and 3-alpha, 6-beta, 7-beta, 12-alpha-tetrahydroxy-5-beta-cholan-24-oic acids, were identified in all amniotic fluid (four samples) and urine (six samples) from adult patients with cholestatic liver disease by gas-liquid chromatography/mass spectrometry. For the certain identification of these bile acids in the biologic samples, the chemical syntheses of 3-alpha, 6-beta, 7-alpha, 12-alpha- and 3-alpha, 6-beta, 7-beta, 12-alpha-tetrahydroxy-5-beta-cholan-24-oic acids were conducted.
• KUROSAWA, TAKAO;MAHARA, REIJIRO;NITTONO, HIROSHI;TOHMA, MASAHIKO, CHEM. AND PHARM. BULL., 37,(1989) N, C. 557-559
  作者：KUROSAWA, TAKAO、MAHARA, REIJIRO、NITTONO, HIROSHI、TOHMA, MASAHIKO

  DOI：——

  日期：——