(5R)-5-[(3R,5S,7R,8R,9S,10S,13R,14S,17R)-3,7-二羟基-10,13-二甲基-2,3,4,5,6,7,8,9,11,12,14,15,16,17-十四氢-1H-环戊二烯并[a]菲-17-基]己酸 | 38636-78-1

• 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: (5R)-5-[(3R,5S,7R,8R,9S,10S,13R,14S,17R)-3,7-二羟基-10,13-二甲基-2,3,4,5,6,7,8,9,11,12,14,15,16,17-十四氢-1H-环戊二烯并[a]菲-17-基]己酸
• 英文名称: 3α,7α-dihydroxy-26,27-dinor-5β-cholestan-25-oic acid
• 英文别名: 3α,7α-dihydroxy-5β-cholane-24-carboxylic acid；chenodeoxycholic acid；25-Homo-chenodesoxycholsaeure；Homochenodeoxycholic acid；(5R)-5-[(3R,5S,7R,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]hexanoic acid
• CAS: 38636-78-1
• 化学式: C₂₅H₄₂O₄
• 分子量: 406.606
• InChiKey: ZKKGBMOMGYRROF-IFJDUOSNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (5R)-5-[(3R,5S,7R,8R,9S,10S,13R,14S,17R)-3,7-二羟基-10,13-二甲基-2,3,4,5,6,7,8,9,11,12,14,15,16,17-十四氢-1H-环戊二烯并[a]菲-17-基]己酸 在 盐酸 、 甲基碘化镁 、 4-异丙基甲苯 、 镍 、 potassium tri-sec-butyl-borohydride 、 2,2-二甲氧基丙烷 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 31.0h， 生成 5α-cholestane-3α,7α,25-triol
  参考文献：
  名称：

  Bile acids. LXIV. Synthesis of 5α-cholestane-3α,7α,25-triol and esters of new 5α-bile acids

  摘要：

  Interest in the structural requirements of a sterol or bile acid for maximal activity by an hepatic microsomal steroid 12 alpha-hydroxylase prompted the preparation of 5 alpha-cholestane-3 alpha, 7 alpha, 25-triol and 5 alpha-analogs of 3 alpha, 7 alpha-dihydroxy-5 beta-cholane-24-carboxylic acid. Methyl 3 alpha, 7 alpha-dihydroxy-5 beta-cholane-24-carboxylate derived from methyl chenodeoxycholate via the Arndt-Eistert reaction was allomerized with Raney nickel in boiling p-cymene to provide a number of product of which methyl 3, 7-dioxo-5 beta- and 5 alpha-cholane-24-carboxylates, methyl 3-oxo-7 alpha-hydroxy-5 beta-and 5 alpha-cholane-24-carboxylates, were identified. Reduction with K-Selectride of methyl 3-oxo-7 alpha-hydroxy-5 beta-cholane-24-carboxylate, provided a high yield of methyl 3 alpha, 7 alpha-dihydroxy-5 alpha-cholane-24-carboxylate. Treatment of this ester with an excess of methyl magnesium iodide afforded 5 alpha-cholestane-3 alpha, 7 alpha, 25-triol. The products were characterized by thin-layer and gas liquid chromatography, proton resonance, infrared and mass spectrometry.

  DOI：

  10.1016/0039-128x(81)90080-5
• 作为产物：
  描述：

  生成 (5R)-5-[(3R,5S,7R,8R,9S,10S,13R,14S,17R)-3,7-二羟基-10,13-二甲基-2,3,4,5,6,7,8,9,11,12,14,15,16,17-十四氢-1H-环戊二烯并[a]菲-17-基]己酸
  参考文献：
  名称：

  Mehrwertige Alkohole aus Sterinen und Sterinderivaten，VI斯特雷德米特Strecturmerkmalen des Ecdysons und der Elatericine

  摘要：

  AUS Litho-，Desoxy- UNDChenodesoxycholsäure（1A - C ^）wurden黚死Homosäuren 5A - Ç模具叔-C 25 -Carbinole 7A - Ç dargestellt。位于Das Ecdyson-Analoge Produkt 18b umwandeln中的胆固醇。Hyodesoxy- UNDHomohyodesoxycholsäurewurden裸片Tetrole部33a，b übergeführt。Aus 34a – d沸腾的硬脂酸酯37a – d mit diosphenolischer Struktur gewonnen。

  DOI：

  10.1002/jlac.19727580109

文献信息

• Mehrwertige Alkohole aus Sterinen und Sterinderivaten, VI Steroide mit Strukturmerkmalen des Ecdysons und der Elatericine
  作者：Hans Lettré、Jürgen Greiner、Klaus Rutz、Lothar Hofmann、Alfons Egle、Wilfried Bieger

  DOI：10.1002/jlac.19727580109

  日期：1972.7.12

  Aus Litho-, Desoxy- und Chenodesoxycholsäure (1a – c) wurden über die Homosäuren 5a – c die tert.-C25-Carbinole 7a – c dargestellt. Cholesterin ließ sich in das Ecdyson-analoge Produkt 18b umwandeln. Hyodesoxy- und Homohyodesoxycholsäure wurden in die Tetrole 33a, b übergeführt. Aus 34a – d wurden die Steroide 37a – d mit diosphenolischer Struktur gewonnen.

  AUS Litho-，Desoxy- UNDChenodesoxycholsäure（1A - C ^）wurden黚死Homosäuren 5A - Ç模具叔-C 25 -Carbinole 7A - Ç dargestellt。位于Das Ecdyson-Analoge Produkt 18b umwandeln中的胆固醇。Hyodesoxy- UNDHomohyodesoxycholsäurewurden裸片Tetrole部33a，b übergeführt。Aus 34a – d沸腾的硬脂酸酯37a – d mit diosphenolischer Struktur gewonnen。
• Bile Acid Derived PET-Based Cation Sensors: Molecular Structure Dependence of their Sensitivity
  作者：Uday Maitra、Suvadeep Nath

  DOI：10.1002/asia.200900026

  日期：2009.6.2

  Sensitive sensors: A general strategy of designing a PET cation sensor using Bile acids as scaffolds has been discussed. Keeping the basic molecular structure the same, different bile acid based fluoroionophores were prepared in order to achieve the highest sensitivity toward the metal ions. The dependence of sensitivity on the molecular structure has been studied.

  敏感传感器：讨论了使用胆汁酸作为支架设计 PET 阳离子传感器的一般策略。保持基本分子结构相同，制备了不同的基于胆汁酸的氟离子载体，以实现对金属离子的最高灵敏度。已经研究了灵敏度对分子结构的依赖性。
• Bile alcohols function as the ligands of membrane-type bile acid-activated G protein-coupled receptor
  作者：Yusuke Iguchi、Masafumi Yamaguchi、Hiroyuki Sato、Kenji Kihira、Tomoko Nishimaki-Mogami、Mizuho Une

  DOI：10.1194/jlr.m004051

  日期：2010.6

  TGR5 is a G protein-coupled receptor that is activated by bile acids, resulting in an increase in cAMP levels and the subsequent modulation of energy expenditure in brown adipose tissue and muscle. Therefore, the development of a TGR5-specific agonist could lead to the prevention and treatment of various metabolic disorders related to obesity. In the present study, we evaluated the ability of bile alcohols, which are structurally and physiologically similar to bile acids and are produced as the end products of cholesterol catabolism in evolutionarily primitive vertebrates, to act as TGR5 agonists. In a cell-based reporter assay and a cAMP production assay performed in vitro, most bile alcohols with a side chain containing hydroxyl group(s) were highly efficacious agonists for TGR5 comparable to its most potent ligand in the naturally occurring bile acid, lithocholic acid. However, the abilities of the bile alcohols to activate TGR5 varied with the position and number of the hydroxyl substituent in the side chain. Additionally, the conformation of the steroidal nucleus of bile alcohols is also important for its activity as a TGR5 agonist. Thus, we have provided new insights into the structure-activity relationships of bile alcohols as TGR5 agonists.-Iguchi, Y., M. Yamaguchi, H. Sato, K. Kihira, T. Nishimaki-Mogami, and M. Une. Bile alcohols function as the ligands of membrane-type bile acid-activated G protein-coupled receptor. J. Lipid Res. 2010. 51: 1432-1441.
• METHOD FOR DETERMINING IN VITRO BIOEQUIVALENCE OF A SUCRALFATE SUSPENSION SAMPLE TO A SUCRALFATE SUSPENSION REFERENCE LISTED DRUG (RLD)
  申请人：Clayton Pharmaceuticals LLC

  公开号：EP3423829B1

  公开（公告）日：2020-10-28
• New bile alcohols — synthesis of 5β-cholestane-3α, 7α, 25-triol and 5β-cholestane-3α, 7α, 25-24(14C)-triol1
  作者：Bertram I. Cohen、G.S. Tint、Taiju Kuramoto、Erwin H. Mosbach

  DOI：10.1016/0039-128x(75)90093-8

  日期：1975.3

  the diformoxy derivative (II) using formic acid. Reaction of II with thionyl chloride yielded the acid chloride which was treated with diazomethane (CH 2 N 2 or 14 CH 2 N 2 ) to produce 3ga, 7α-diformoxy-24-oxo-25-diazo-25-homocholane (III, A or B). 25-Homochenodeoxycholic acid (IV, A or B) was formed from III by means of the Wolff rearrangement of the Arndt-Eistert synthesis. The methyl ester of V (A

  摘要 5β-胆甾烷-3α, 7α, 25-三醇和5β-胆甾烷-3α, 7α, 25-24( 14 C)-三醇由3α, 7α-二羟基-5β-胆酸（鹅去氧胆酸）合成。鹅去氧胆酸使用甲酸转化为二甲氧基衍生物(II)。II 与亚硫酰氯反应生成酰氯，用重氮甲烷（CH 2 N 2 或 14 CH 2 N 2 ）处理生成 3ga, 7α-diformoxy-24-oxo-25-diazo-25-homocholane (III, A或 B)。25-高鹅脱氧胆酸（IV、A 或 B）是通过 Arndt-Eistert 合成的沃尔夫重排由 III 形成的。V(A或B)的甲酯在醚中用甲基碘化镁处理以提供所需的三醇VI(A和B)。三醇通过质谱和元素分析进行​​鉴定，并通过薄层色谱和气液色谱进行表征。3α、7α、