methyl 3β,7β-dihydroxycholanate | 73465-45-9

• 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: methyl 3β,7β-dihydroxycholanate
• 英文别名: methyl 3β,7β-dihydroxy-5β-cholan-24-oate；methyl (3β,5β,7β)-3,7-dihydroxycholan-24-oate；3beta,7beta-Dihydroxy-5beta-cholan-24-oic acid methyl ester；methyl (4R)-4-[(3S,5S,7S,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]pentanoate
• CAS: 73465-45-9
• 化学式: C₂₅H₄₂O₄
• 分子量: 406.606
• InChiKey: GRQROVWZGGDYSW-LWNNJCQBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 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：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3β,7β-dihydroxycholanate 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 以87%的产率得到(4R)-4-[(3S,5S,7S,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-环戊并[a]菲-17-基]戊酸
  参考文献：
  名称：

  Exploitation of Cholane Scaffold for the Discovery of Potent and Selective Farnesoid X Receptor (FXR) and G-Protein Coupled Bile Acid Receptor 1 (GP-BAR1) Ligands

  摘要：

  Nuclear and G-protein coupled receptors are considered major targets for drug discovery. FXR and GP-BAR1, two bile acid-activated receptors, have gained increasing consideration as druggable receptors. Because endogenous bile acids often target both receptor families, the development of selective ligands has been proven difficult, exposing patients to side effects linked to an unwanted activation of one of the two receptors. In the present study, we describe a novel library of semisynthetic bile acid derivatives obtained by modifications on the cholane scaffold. The pharmacological characterization of this library led to the discovery of 7a-hydroxy-5 beta-cholan-24-sulfate (7), 6 beta-ethyl-3a,7 beta-dihydroxy-5 beta-cholan-24-ol (EUDCOH, 26), and 6a-ethyl-3a, 7a-dihydroxy-24-nor-5 beta-cholan-23-ol (NorECDCOH, 30) as novel ligands for FXR and GP-BAR1 that might hold utility in the treatment of FXR and GP-BAR1 mediated disorders.

  DOI：

  10.1021/jm501273r
• 作为产物：
  描述：

  methyl 3α-tosyloxy-7α-hydroxy-5β-cholan-24-oate 在 吡啶 、 盐酸 、 aluminum oxide 、 potassium superoxide 、 18-冠醚-6 作用下， 以 乙二醇二甲醚 、 二甲基亚砜 、 苯 为溶剂， 反应 20.0h， 生成 methyl 3β,7β-dihydroxycholanate
  参考文献：
  名称：

  Potential bile acid metabolites. 6. Stereoisomeric 3,7-dihydroxy-5.beta.-cholanic acids

  摘要：

  DOI：

  10.1021/jo00136a030

文献信息

• Hydroxysteroid Dehydrogenase-Catalyzed Highly Regio-, Chemo-, and Enantioselective Hydrogenation of 3-Keto in Steroids
  作者：Chunling Zeng、Shitang Xu、Jie Shen、Saijie Zhao、Xinhua Xu、Lifen Peng

  DOI：10.1021/acs.orglett.3c03557

  日期：2024.1.12

  A highly selective hydrogenation of 3-keto in steroids to 3-hydroxyl steroids catalyzed by hydroxysteroid dehydrogenases (HSDHs) was demonstrated. The Ct3α-HSDH-catalyzed hydrogenation generated 3α-hydroxyl steroids as the main enantiopure isomers in high yields, while the Ss3β-HSDH catalytic system afforded 3β-hydroxyl steroids in excellent yields. In both catalytic systems, the hydrogenation proceeded

  证明了在羟基类固醇脱氢酶 (HSDH) 的催化下，类固醇中的 3-酮基可以高度选择性地氢化为 3-羟基类固醇。 Ct3α-HSDH催化的氢化反应以高产率产生了作为主要对映体纯异构体的3α-羟基类固醇，而Ss3β-HSDH催化体系则以优异的产率产生了3β-羟基类固醇。在两种催化体系中，氢化反应在 3-酮基上进行区域选择性，7-、11-、17-和 20-酮基几乎未反应，并且在 C=C 键和酯基未受攻击的情况下进行化学选择性氢化。我们的HSDH促进的氢化反应具有区域选择性、化学选择性和对映选择性高、收率好、条件温和、底物范围广、适合克级合成等优点。值得注意的是，通过我们的氢化方法，可以轻松、高产地获得脱氢表雄酮、布烯醇酮和阿法沙酮等生物活性分子。
• Chang, Frederic C., Synthetic Communications, 1981, vol. 11, # 11, p. 875 - 880
  作者：Chang, Frederic C.

  DOI：——

  日期：——
• Potential bile acid metabolites. 6. Stereoisomeric 3,7-dihydroxy-5.beta.-cholanic acids
  作者：Takashi Iida、Frederic C. Chang

  DOI：10.1021/jo00136a030

  日期：1982.7
• Exploitation of Cholane Scaffold for the Discovery of Potent and Selective Farnesoid X Receptor (FXR) and G-Protein Coupled Bile Acid Receptor 1 (GP-BAR1) Ligands
  作者：Carmen Festa、Barbara Renga、Claudio D’Amore、Valentina Sepe、Claudia Finamore、Simona De Marino、Adriana Carino、Sabrina Cipriani、Maria Chiara Monti、Angela Zampella、Stefano Fiorucci

  DOI：10.1021/jm501273r

  日期：2014.10.23

  Nuclear and G-protein coupled receptors are considered major targets for drug discovery. FXR and GP-BAR1, two bile acid-activated receptors, have gained increasing consideration as druggable receptors. Because endogenous bile acids often target both receptor families, the development of selective ligands has been proven difficult, exposing patients to side effects linked to an unwanted activation of one of the two receptors. In the present study, we describe a novel library of semisynthetic bile acid derivatives obtained by modifications on the cholane scaffold. The pharmacological characterization of this library led to the discovery of 7a-hydroxy-5 beta-cholan-24-sulfate (7), 6 beta-ethyl-3a,7 beta-dihydroxy-5 beta-cholan-24-ol (EUDCOH, 26), and 6a-ethyl-3a, 7a-dihydroxy-24-nor-5 beta-cholan-23-ol (NorECDCOH, 30) as novel ligands for FXR and GP-BAR1 that might hold utility in the treatment of FXR and GP-BAR1 mediated disorders.