methyl 3α,12α-bis(chloroacetoxy)-5β-cholan-24-oate

• 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 3α,12α-bis(chloroacetoxy)-5β-cholan-24-oate
• 英文别名: methyl 3α,12α-bis(chloroacetyloxy)-5β-deoxycholan-24-oate；methyl 3α,12α-di(2'-chloro)acetoxy-5β-deoxycholan-24-oate；methyl (4R)-4-[(3R,5R,8R,9S,10S,12S,13R,14S,17R)-3,12-bis[(2-chloroacetyl)oxy]-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
• 化学式: C₂₉H₄₄Cl₂O₆
• 分子量: 559.571
• InChiKey: REVGJHPCJCCJOR-QIXZANHSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  78.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 3α,12α-bis(chloroacetoxy)-5β-cholan-24-oate 在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以95%的产率得到methyl 3α,12α-bis(azidoacetoxy)-5β-cholan-24-oate
  参考文献：
  名称：

  用于分子镊金属离子识别的脱氧胆酸1,2,3-三唑衍生物的合成

  摘要：

  已经使用点击化学方法通过 3,12-叠氮酯合成了一系列基于脱氧胆酸甲酯的 [1,2,3-三唑并乙酰] 酯的分子镊子金属受体。它们的结构通过1H NMR、IR、MS光谱和元素分析表征。通过紫外-可见光谱滴定检查它们的结合特性。初步结果表明，该类型分子镊对金属离子具有良好的识别能力。

  DOI：

  10.3184/174751912x13352834523329
• 作为产物：
  描述：

  去氧胆酸 在 吡啶 、 盐酸 、 4-二甲氨基吡啶 作用下， 以 水 、 甲苯 为溶剂， 反应 24.5h， 生成 methyl 3α,12α-bis(chloroacetoxy)-5β-cholan-24-oate
  参考文献：
  名称：

  胆汁酸-他莫昔芬偶联物在乳腺癌治疗中的设计，合成及机理研究

  摘要：

  我们已经合成了两个系列的胆汁酸他莫昔芬共轭物，使用了三种胆汁酸石胆酸（LCA），脱氧胆酸（DCA）和胆酸（CA）。这些胆汁酸-他莫昔芬共轭物具有1、2和3个他莫昔芬分子，这些分子与胆汁酸的羟基相连，在胆汁酸的尾部具有游离酸和胺官能团。在体外这些胆汁酸他莫昔芬结合物的抗癌活性表明，游离胺首基的基于胆酸-他莫昔芬结合物（CA-担3 -Am与母体药物他莫昔芬和其他基于酸和胺头基的胆汁酸-他莫昔芬结合物相比，）是最有效的抗癌结合物。带有三个他莫昔芬分子的胆酸-他莫昔芬共轭物（CA-Tam 3 -Am）在雌激素受体+ ve和雌激素受体-ve乳腺癌细胞系中均显示出增强的抗癌活性。CA-Tam 3 -Am的增强的抗癌活性是由于更有利的不可逆的静电相互作用，随后这些共轭物插入到膜脂质的疏水核中，导致膜流动性增加。基于膜联蛋白-FITC的FACS分析表明细胞发生凋亡，而细胞周期分析表明细胞停滞在sub G

  DOI：

  10.1021/bc300664k

文献信息

• Design, Synthesis, and Mechanistic Investigations of Bile Acid–Tamoxifen Conjugates for Breast Cancer Therapy
  作者：Vedagopuram Sreekanth、Sandhya Bansal、Rajender K. Motiani、Somanath Kundu、Sravan Kumar Muppu、Tapodhara Datta Majumdar、Kuppusamy Panjamurthy、Sagar Sengupta、Avinash Bajaj

  DOI：10.1021/bc300664k

  日期：2013.9.18

  shows enhanced anticancer activities in both estrogen receptor +ve and estrogen receptor −ve breast cancer cell lines. The enhanced anticancer activity of CA-Tam3-Am is due to more favorable irreversible electrostatic interactions followed by intercalation of these conjugates in hydrophobic core of membrane lipids causing increase in membrane fluidity. Annexin-FITC based FACS analysis showed that cells

  我们已经合成了两个系列的胆汁酸他莫昔芬共轭物，使用了三种胆汁酸石胆酸（LCA），脱氧胆酸（DCA）和胆酸（CA）。这些胆汁酸-他莫昔芬共轭物具有1、2和3个他莫昔芬分子，这些分子与胆汁酸的羟基相连，在胆汁酸的尾部具有游离酸和胺官能团。在体外这些胆汁酸他莫昔芬结合物的抗癌活性表明，游离胺首基的基于胆酸-他莫昔芬结合物（CA-担3 -Am与母体药物他莫昔芬和其他基于酸和胺头基的胆汁酸-他莫昔芬结合物相比，）是最有效的抗癌结合物。带有三个他莫昔芬分子的胆酸-他莫昔芬共轭物（CA-Tam 3 -Am）在雌激素受体+ ve和雌激素受体-ve乳腺癌细胞系中均显示出增强的抗癌活性。CA-Tam 3 -Am的增强的抗癌活性是由于更有利的不可逆的静电相互作用，随后这些共轭物插入到膜脂质的疏水核中，导致膜流动性增加。基于膜联蛋白-FITC的FACS分析表明细胞发生凋亡，而细胞周期分析表明细胞停滞在sub G
• Deciphering the role of charge, hydration, and hydrophobicity for cytotoxic activities and membrane interactions of bile acid based facial amphiphiles
  作者：Manish Singh、Ashima Singh、Somanath Kundu、Sandhya Bansal、Avinash Bajaj

  DOI：10.1016/j.bbamem.2013.04.003

  日期：2013.8

  We synthesized four cationic bile add based facial amphiphiles featuring trimethyl ammonium head groups. We evaluated the role of these amphiphiles for cytotoxic activities against colon cancer cells and their membrane interactions by varying charge, hydration and hydrophobicity. The singly charged cationic Lithocholic add based amphiphile (LCA-TMA(1)) is most cytotoxic, whereas the triply charged cationic Cholic add based amphiphile (CA-TMA(3)) is least cytotoxic. Light microscopy and Annexin-FITC assay revealed that these facial amphiphiles caused late apoptosis. In addition, we studied the interactions of these amphiphiles with model membrane systems by Prodan-based hydration, DPH-based anisotropy, and differential scanning calorimetry. LCA-TMA(1) is most hydrophobic with a hard charge causing efficient dehydration and maximum perturbations of membranes thereby facilitating translocation and high cytotoxicity against colon cancer cells. In contrast, the highly hydrated and multiple charged CA-TMA(3) caused least membrane perturbations leading to low translocation and less cytotoxicity. As expected, Chenodeoxycholic add and Deoxycholic add based amphiphiles (CDCA-TMA(2), DCA-TMA(2)) featuring two charged head groups showed intermediate behavior. Thus, we deciphered that charge, hydration, and hydrophobicity of these amphiphiles govern membrane interactions, translocation, and resulting cytoxicity against colon cancer cells. (C) 2013 Elsevier B.V. All rights reserved.
• Design, synthesis, and micellar properties of bile acid dimers and oligomers linked with a 1,2,3-triazole ring
  作者：Nilkanth G. Aher、Vandana S. Pore、Sachin P. Patil

  DOI：10.1016/j.tet.2007.10.042

  日期：2007.12

  1,3-Dipolar cycloaddition of propargyl esters of bile acids to azide group attached at different positions of bile acids gave dimers, trimer, and tetramer linked with 1,2,3-triazole. These dimeric and oligomeric structures were able to solubilize hydrophilic dye-cresol red, in nonpolar solvent. (c) 2007 Elsevier Ltd. All rights reserved.
• The Synthesis of 1,2,3-Triazole Derivatives of Deoxycholic Acid for Molecular Tweezer Metal Ion Recognition
  作者：Yuyu Cheng、Zhigang Zhao、Min Liu、Yongle Peng

  DOI：10.3184/174751912x13352834523329

  日期：2012.6

  series of molecular tweezer metal receptors based on [1,2,3-triazolo-acetyl]esters of methyl deoxycholate have been synthesised via the 3,12-azidoester using a click chemistry method. Their structures were characterized by 1H NMR, IR, MS spectra and elemental analysis. Their binding properties were examined by UV-Vis spectra titration. The preliminary results indicate that this type of molecular tweezers

  已经使用点击化学方法通过 3,12-叠氮酯合成了一系列基于脱氧胆酸甲酯的 [1,2,3-三唑并乙酰] 酯的分子镊子金属受体。它们的结构通过1H NMR、IR、MS光谱和元素分析表征。通过紫外-可见光谱滴定检查它们的结合特性。初步结果表明，该类型分子镊对金属离子具有良好的识别能力。
• Bile acid amphiphiles with tunable head groups as highly selective antitubercular agents
  作者：Sandhya Bansal、Manish Singh、Saqib Kidwai、Priyanshu Bhargava、Ashima Singh、Vedagopuram Sreekanth、Ramandeep Singh、Avinash Bajaj

  DOI：10.1039/c4md00303a

  日期：——

  Hard-charged amphiphiles are highly selective against mycobacteria, whereas soft-charged amphiphiles are active against Gram-positive and Gram-negative bacteria.

  硬电荷两性分子对分枝杆菌具有高度选择性，而软电荷两性分子对革兰氏阳性和革兰氏阴性细菌具有活性。