methyl 3α-(2'-chloro)acetoxy-5β-lithocholan-24-oate | 26632-52-0

• 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
• 英文名称: methyl 3α-(2'-chloro)acetoxy-5β-lithocholan-24-oate
• 英文别名: methyl 3α-chloroacetyloxy-5β-lithocholan-24-oate；methyl 3α-(chloroacetoxy)-5β-cholan-24-oate；methyl 3α-chloroacetoxy-5β-cholan-24-oate
• CAS: 26632-52-0
• 化学式: C₂₇H₄₃ClO₄
• 分子量: 467.089
• InChiKey: WURPSZDHLJNCTG-RMXYKXGFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.39
• 重原子数：
  32.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  52.6
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl 3α-(2'-chloro)acetoxy-5β-lithocholan-24-oate 以 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 120.0h， 生成
  参考文献：
  名称：

  胆酸衍生的 Gemini 两亲物可以根除界间多微生物生物膜和伤口感染

  摘要：

  生物膜感染主要由金黄色葡萄球菌等革兰氏阳性菌（GPB）、铜绿假单胞菌等革兰氏阴性菌（GNB）和白色念珠菌等真菌引起。这些感染导致抗生素耐受性，这些微生物的共生相互作用对慢性感染构成严重威胁。针对生物膜感染的治疗方法仅限于根除 20-30% 的感染。在这里，我们展示了使用石胆酸、脱氧胆酸和胆酸合成一系列胆汁酸衍生分子，其中两个胆汁酸分子通过具有不同间隔长度的 3'-羟基或 24'-羧基末端（三亚甲基，五亚甲基、八亚甲基和十二亚甲基）。我们的结构-活性关系研究表明， G21是一种胆酸衍生的双子两亲物，具有通过 C24 位置连接的三亚甲基间隔基，是一种广谱抗菌剂。生化研究表明， G21与 GPB、GNB 和真菌的带负电荷的脂磷壁酸、脂多糖和磷脂酰胆碱部分相互作用，并破坏微生物细胞膜。我们进一步证明， G21可以根除多种微生物生物膜和伤口感染，并防止细菌和真菌产生耐药性。因此，我们的研究结果揭示了

  DOI：

  10.1021/acsinfecdis.3c00369
• 作为产物：
  描述：

  石胆酸 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-(2'-chloro)acetoxy-5β-lithocholan-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

• CuAAC Synthesis and Anion Binding Properties of Bile Acid Derived Tripodal Ligands
  作者：Dmitry A. Erzunov、Gennadij V. Latyshev、Alexey D. Averin、Irina P. Beletskaya、Nikolay V. Lukashev

  DOI：10.1002/ejoc.201500835

  日期：2015.10

  24-5β-cholanetriazolyl derivatives of phosphorus acids, which contained anion-binding triazolium sites and hydrophobic cholane residues. The influence of the location of the triazolium moiety (in 3α-, 3β-position) on fluoride-ion complexation was investigated. The anion-binding properties of tris(triazolium) ligands were studied for a series of inorganic and organic anions and high complexation constants were

  铜催化的叠氮化物-炔环加成反应用于制备一系列磷酸的双和三-3-和 24-5β-胆烷三唑基衍生物，其中含有阴离子结合的三唑鎓位点和疏水性胆烷残基。研究了三唑鎓部分的位置（在 3α-、3β-位）对氟离子络合的影响。研究了一系列无机和有机阴离子的三（三唑鎓）配体的阴离子结合特性，并观察到氟离子、硫酸氢根和苯甲酸根阴离子的高络合常数。
• 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。
• Synthesis, structure–activity relationship, and mechanistic investigation of lithocholic acidamphiphiles for colon cancer therapy
  作者：Manish Singh、Sandhya Bansal、Somanath Kundu、Priyanshu Bhargava、Ashima Singh、Rajender K. Motiani、Radhey Shyam、Vedagopuram Sreekanth、Sagar Sengupta、Avinash Bajaj

  DOI：10.1039/c4md00223g

  日期：——

  We report the enhanced anticancer activities of lithocholic acid amphiphiles possessing different charged head group for colon cancer therapy.

  我们报告了不同带电头基的毒胆酸两性分子在结肠癌治疗中的增强抗癌活性。
• A practical synthesis and spectroscopic study of new potentially biologically active S-lithocholic acid-substituted derivatives of 2-thiouracil
  作者：Tomasz Pospieszny、Izabela Małecka、Zdzisław Paryzek

  DOI：10.1016/j.tetlet.2010.05.094

  日期：2010.8

  Five new S-3 alpha-acetoxy-5 beta-lithocholic acid methyl ester-substituted derivatives of 2-thiouracil and 6-methyl-2-thiouracil have been prepared. 5-Morpholino-methyl-2-thiouracil, 5-piperidinomethyl-2-thiouracil, and 5-(4-methylpiperidino)methyl-2-thiouracil have been obtained via the Mannich reaction between 6-methyl-2-thiouracil, paraformaldehyde, and the cyclic secondary amines morpholine, piperdine, or 4-methylpiperidine in ethanol. The structures of the compounds were confirmed by spectral ((1)H NMR, (13)C NMR, and FT-IR) analyses and mass spectrometry. Estimation of the pharmacotherapeutic potential has been accomplished for the synthesized compounds on the basis of Prediction of Activity Spectra for Substances (PASS). (C) 2010 Elsevier Ltd. All rights reserved.
• 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.