3α,6α,7α,12α-tetrahydroxy-5β-cholan-24-oic acid | 80875-92-9

• 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,7α,12α-tetrahydroxy-5β-cholan-24-oic acid
• 英文别名: 3alpha,6alpha,7alpha,12alpha-Tetrahydroxy-5beta-cholan-24-oic Acid；(4R)-4-[(3R,5R,6R,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: 80875-92-9
• 化学式: C₂₄H₄₀O₆
• 分子量: 424.578
• InChiKey: COCMFMBNEAMQMA-NQTCFNIESA-N

物化性质

• 熔点：
  161-163 °C
• 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：

  3α,6α,7α,12α-tetrahydroxy-5β-cholan-24-oic acid 在 吡啶 、 N-羟基丁二酰亚胺 、 N,N'-二环己基碳二亚胺 、 sodium hydroxide 作用下， 反应 2.5h， 生成 2-[[(4R)-4-[(3R,5R,6R,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]pentanoyl]amino]ethanesulfonic acid
  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
• 作为产物：
  描述：

  胆酸 在 4-二甲氨基吡啶 吡啶 、 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 zinc(II) tetrahydroborate 、 溴 、 碳酸氢钠 、 溶剂黄146 、 potassium hydroxide 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 苯 为溶剂， 反应 171.0h， 生成 3α,6α,7α,12α-tetrahydroxy-5β-cholan-24-oic acid
  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

• An efficient synthesis of 4β- and 6α- hydroxylated bile acids
  作者：Teruki Yoshimura、Reijiro Mahara、Takao Kurosawa、Shigeo Ikegawa、Masahiko Tohma

  DOI：10.1016/0039-128x(93)90052-o

  日期：1993.2

  bile acids has been developed. It involved a highly stereoselective acetoxylation at the 4β and 6α positions of 3- and 7-oxo bile acids, respectively, with lead tetraacetate in the presence of boron trifluoride etherate in acetic acid. Reduction of the resulting α-acetoxy ketones with sodium borohydride or tert-butylamine borane complex, and alkaline hydrolysis, provided the desired bile acids in good

  摘要 开发了一种制备 4β- 和 6α- 羟基化胆汁酸的有效方法。它涉及分别在 3- 和 7- 氧代胆汁酸的 4β 和 6α 位的高度立体选择性乙酰氧基化，在乙酸中存在三氟化硼醚合物的情况下，四乙酸铅。用硼氢化钠或叔丁胺硼烷络合物还原生成的 α-乙酰氧基酮，并进行碱性水解，以良好的收率提供所需的胆汁酸。（类固醇 58:–58, 1993）
• Chemical Synthesis of (22E)-3.ALPHA.,6.ALPHA.,7.ALPHA.,12.ALPHA.-Tetrahydroxy-5.BETA.-chol-22-en-24-oic Acid and Its N-Acylamidated Conjugates with Glycine or Taurine: Precursors of the [22,23-3H] Labelled Tracers
  作者：Shoujiro Ogawa、Yuuki Adachi、Genta Kakiyama、Miki Shimada、Nariyasu Mano、Junichi Goto、Takashi Iida

  DOI：10.1248/cpb.58.1103

  日期：——

  (22E)-3α,6α,7α,12α-Tetrahydroxy-5β-chol-22-en-24-oic acid and its N-acylamidated conjugates with glycine or taurine were synthesized from cholic acid. The key reactions employed are: 1) degradation of the side chain in intermediary C24 3α,6α,7α,12α-tetrahydroxylated bile acid to the corresponding C22 23,24-dinor-aldehyde, followed by Wittig reaction with methyl (triphenylphosphoranylidene)acetate and 2) N-acylamidation of the unconjugated tetrahydroxy-Δ22-5β-cholenoic acid with glycine (or taurine) in the presence of diethylphosphorocyanide and triethylamine as coupling reagents.

  以胆酸为原料合成了 (22E)-3α,6α,7α,12α-四羟基-5β-胆-22-烯-24-酸及其与甘氨酸或牛磺酸的 N-酰基酰胺化共轭物。所采用的关键反应是1) 将中间体 C24 3α,6α,7α,12α-四羟基胆酸中的侧链降解为相应的 C22 23,24-二甲醛、2) 未结合的四羟基-Δ22-5β-胆烯酸与甘氨酸（或牛磺酸）在二乙基磷腈和三乙胺作为偶联试剂的存在下发生 N-酰氨基化反应。
• 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。
• Potential bile acid metabolites. 16. Synthesis of stereoisomeric 3α,6,7,12α-tetrahydroxy-5β-cholanoic acids
  作者：Iida Takashi、Komatsubara Ichiro、Yoda Sciichiro、Goto Junichi、Nambara Toshio、Frederic C. Chang

  DOI：10.1016/0039-128x(90)90048-g

  日期：1990.12

  possible stereoisomeric 3 alpha,6,7,12 alpha-tetrahydroxy-5 beta-cholanoic acids (and their methyl esters), one of which (3 alpha,6 alpha 7 beta,12 alpha) is new, and some related compounds are described. In addition, the 5 alpha-epimer of the new acid was obtained. The final products were obtained in high purity for use as reference compounds in the analysis of bile acids in human biologic samples

  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。
• 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。