lithocholic acid methyl ester | 1148117-65-0

• 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: lithocholic acid methyl ester
• 英文别名: methyl 3α-chlorocarbonyloxy-5β-cholan-24-oate；methyl (4R)-4-[(3R,5R,8R,9S,10S,13R,14S,17R)-3-carbonochloridoyloxy-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: 1148117-65-0
• 化学式: C₂₆H₄₁ClO₄
• 分子量: 453.062
• InChiKey: CIGFZAQPHDCOPF-OETIFKLTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  lithocholic acid methyl ester 在 吡啶 、 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 15.0h， 生成
  参考文献：
  名称：

  ‘Click’ synthesized sterol-based cationic lipids as gene carriers, and the effect of skeletons and headgroups on gene delivery

  摘要：

  In this work, we have successfully prepared a series of new sterol-based cationic lipids (1-4) via an efficient 'Click' chemistry approach. The pDNA binding affinity of these lipids was examined by EB displacement and agarose-gel retardant assay. The average particle sizes and surface charges of the sterol-based cationic lipids/pDNA lipoplexes were analyzed by dynamic laser light scattering instrument (DLS), and the morphologies of the lipoplexes were observed by atomic force microscopy (AFM). The cytotoxicity of the lipids were examined by MTT and LDH assay, and the gene transfection efficiencies of these lipid carriers were investigated by luciferase gene transfection assay in various cell lines. In addition, the intracellular uptake and trafficking/localization behavior of the Cy3-DNA loaded lipoplexes were preliminarily studied by fluorescence microscopy. The results demonstrated that the pDNA loading capacity, lipoplex particle size, zeta potential and morphology of the sterol lipids/pDNA lipoplexes depended largely on the molecular structure factors including sterol-skeletons and headgroups. Furthermore, the sterol-based lipids showed quite different cytotoxicity and gene transfection efficacy in A549 and HeLa cells. Interestingly, it was found that the cholesterol-bearing lipids 1 and 2 showed 7-10(4) times higher transfection capability than their lithocholate-bearing counterparts 3 and 4 in A549 and HeLa cell lines, suggested that the gene transfection capacity strongly relied on the structure of sterol skeletons. Moreover, the study on the structure-activity relationships of these sterol-based cationic lipid gene carriers provided a possible approach for developing low cytotoxic and high efficient lipid gene carriers by selecting suitable sterol hydrophobes and cationic headgroups. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.08.047
• 作为产物：
  描述：

  三光气 、 3-Alpha-羟基-5-beta-24-胆烷酸甲酯 在 吡啶 作用下， 以 苯 为溶剂， 反应 24.0h， 以82%的产率得到lithocholic acid methyl ester
  参考文献：
  名称：

  胆汁酸甲酯O-氯羰基衍生物的合成及光谱表征

  摘要：

  描述了一系列胆汁酸甲酯的 O-氯羰基衍生物的合成。甾体氯甲酸酯是通过相应的羟基衍生物与三光气-吡啶在苯中于 25°C 反应制备的。O-氯羰基衍生物通过光谱方法表征。

  DOI：

  10.3184/174751914x14114811614153

文献信息

• A new approach to steroid dimers and macrocycles by the reaction of 3-chlorocarbonyl derivatives of bile acids with O,O-, N,N-, and S,S-dinucleophiles
  作者：Zdzisław Paryzek、Roman Joachimiak、Monika Piasecka、Tomasz Pospieszny

  DOI：10.1016/j.tetlet.2012.08.151

  日期：2012.11

  The reaction of 3-chlorocarbonyl derivatives of bile acid esters with O,O-, N,N-, and S,S-dinucleophiles provides a general and efficient entry into steroid dimers with bis-carbamate, bis-carbonate, and bis-monothiocarbonate moieties in the linker fragment. The macrocyclization of the bis-carbamate 10 afforded the dimeric and tetrameric cholaphanes, 15 and 16, respectively.

  胆酸酯的3-氯羰基衍生物与O，O-，N，N-和S，S-二亲核试剂的反应提供了一种普遍有效的进入类固醇二聚体的方法，包括双氨基甲酸酯，双碳酸酯和双一硫代碳酸酯接头片段中的部分。双氨基甲酸酯10的大环化分别提供了二聚和四聚胆甾烷15和16。
• ‘Click’ synthesized sterol-based cationic lipids as gene carriers, and the effect of skeletons and headgroups on gene delivery
  作者：Ruilong Sheng、Ting Luo、Hui Li、Jingjing Sun、Zhao Wang、Amin Cao

  DOI：10.1016/j.bmc.2013.08.047

  日期：2013.11

  In this work, we have successfully prepared a series of new sterol-based cationic lipids (1-4) via an efficient 'Click' chemistry approach. The pDNA binding affinity of these lipids was examined by EB displacement and agarose-gel retardant assay. The average particle sizes and surface charges of the sterol-based cationic lipids/pDNA lipoplexes were analyzed by dynamic laser light scattering instrument (DLS), and the morphologies of the lipoplexes were observed by atomic force microscopy (AFM). The cytotoxicity of the lipids were examined by MTT and LDH assay, and the gene transfection efficiencies of these lipid carriers were investigated by luciferase gene transfection assay in various cell lines. In addition, the intracellular uptake and trafficking/localization behavior of the Cy3-DNA loaded lipoplexes were preliminarily studied by fluorescence microscopy. The results demonstrated that the pDNA loading capacity, lipoplex particle size, zeta potential and morphology of the sterol lipids/pDNA lipoplexes depended largely on the molecular structure factors including sterol-skeletons and headgroups. Furthermore, the sterol-based lipids showed quite different cytotoxicity and gene transfection efficacy in A549 and HeLa cells. Interestingly, it was found that the cholesterol-bearing lipids 1 and 2 showed 7-10(4) times higher transfection capability than their lithocholate-bearing counterparts 3 and 4 in A549 and HeLa cell lines, suggested that the gene transfection capacity strongly relied on the structure of sterol skeletons. Moreover, the study on the structure-activity relationships of these sterol-based cationic lipid gene carriers provided a possible approach for developing low cytotoxic and high efficient lipid gene carriers by selecting suitable sterol hydrophobes and cationic headgroups. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthesis and Spectroscopic Characterisation of <i>O</i>-Chlorocarbonyl Derivatives of Bile Acid Methyl Esters
  作者：Iwona Skiera、Zdzisław Paryzek

  DOI：10.3184/174751914x14114811614153

  日期：2014.10

  The synthesis of O-chlorocarbonyl derivatives of a series of bile acid methyl esters is described. The steroidal chloroformate esters were prepared by the reaction of the respective hydroxy derivatives with triphosgene–pyridine in benzene at 25 °C. The O-chlorocarbonyl derivatives were characterised by spectroscopic methods.

  描述了一系列胆汁酸甲酯的 O-氯羰基衍生物的合成。甾体氯甲酸酯是通过相应的羟基衍生物与三光气-吡啶在苯中于 25°C 反应制备的。O-氯羰基衍生物通过光谱方法表征。