tetradecyl 2'-O,3'-O-isopropylidenuridin-5'-yl vinylphosphonate | 1344121-65-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: tetradecyl 2'-O,3'-O-isopropylidenuridin-5'-yl vinylphosphonate
• 英文别名: tetradecyl 2',3'-isopropylideneuridin-5'-yl vinylphosphonate；1-[(3aR,4R,6R,6aR)-6-[[ethenyl(tetradecoxy)phosphoryl]oxymethyl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]pyrimidine-2,4-dione
• CAS: 1344121-65-8
• 化学式: C₂₈H₄₇N₂O₈P
• 分子量: 570.664
• InChiKey: PXTJMIGSIGONBH-XDVJKSQNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  39
• 可旋转键数：
  19
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tetradecyl 2'-O,3'-O-isopropylidenuridin-5'-yl vinylphosphonate 在 盐酸 作用下， 以 甲醇 、 正丁醇 为溶剂， 反应 4.0h， 生成 tetradecyl uridin-5'-yl 2-([3R,4R]-3,4-dihydroxypyrrolidin-1-yl)ethylphosphonate
  参考文献：
  名称：

  Lipophosphonoxins: New Modular Molecular Structures with Significant Antibacterial Properties

  摘要：

  Novel compounds termed lipophosphonoxins were prepared using a simple and efficient synthetic approach. The general structure of lipophosphonoxins consists of four modules: (i) a nucleoside module, (ii) an iminosugar module, (iii) a hydrophobic module (lipophilic alkyl chain), and (iv) a phosphonate linker module that holds together modules i-iii. Lipophosphonoxins displayed significant antibacterial properties against a panel of Gram-positive species, including multiresistant strains. The minimum inhibitory concentration (MIC) values of the best inhibitors were in the 1-12 mu g/mL range, while their cytotoxic concentrations against human cell lines were significantly above this range. The modular nature of this artificial scaffold offers a large number of possibilities for further modifications/exploitation of these compounds.

  DOI：

  10.1021/jm2009343
• 作为产物：
  描述：

  十四醇 、 在 2,4,6-三异丙基苯磺酰氯 作用下， 以 二氯甲烷 为溶剂， 以40%的产率得到tetradecyl 2'-O,3'-O-isopropylidenuridin-5'-yl vinylphosphonate
  参考文献：
  名称：

  Lipophosphonoxins: New Modular Molecular Structures with Significant Antibacterial Properties

  摘要：

  Novel compounds termed lipophosphonoxins were prepared using a simple and efficient synthetic approach. The general structure of lipophosphonoxins consists of four modules: (i) a nucleoside module, (ii) an iminosugar module, (iii) a hydrophobic module (lipophilic alkyl chain), and (iv) a phosphonate linker module that holds together modules i-iii. Lipophosphonoxins displayed significant antibacterial properties against a panel of Gram-positive species, including multiresistant strains. The minimum inhibitory concentration (MIC) values of the best inhibitors were in the 1-12 mu g/mL range, while their cytotoxic concentrations against human cell lines were significantly above this range. The modular nature of this artificial scaffold offers a large number of possibilities for further modifications/exploitation of these compounds.

  DOI：

  10.1021/jm2009343

文献信息

• Lipophosphonoxins, method of their preparation and use
  申请人：Ustav organicke chemie a biochemie AV CR, v.v.i.

  公开号：EP2527351B1

  公开（公告）日：2013-12-11
• Lipophosphonoxins II: Design, Synthesis, and Properties of Novel Broad Spectrum Antibacterial Agents
  作者：Gabriela Seydlová、Radek Pohl、Eva Zborníková、Marcel Ehn、Ondřej Šimák、Natalya Panova、Milan Kolář、Kateřina Bogdanová、Renata Večeřová、Radovan Fišer、Hana Šanderová、Dragana Vítovská、Petra Sudzinová、Jiří Pospíšil、Oldřich Benada、Tomáš Křížek、David Sedlák、Petr Bartůněk、Libor Krásný、Dominik Rejman

  DOI：10.1021/acs.jmedchem.7b00355

  日期：2017.7.27

  The increase in the number of bacterial strains resistant to known antibiotics is alarming. In this study we report the synthesis of novel compounds termed Lipophosphonoxins II (LPPO II). We show that LPPO II display excellent activities against Gram-positive and-negative bacteria, including pathogens and multiresistant strains. We describe their mechanism of action plasmatic membrane pore-forming activity selective for bacteria. Importantly, LPPO II neither damage nor cross the eukaryotic plasmatic membrane at their bactericidal concentrations. Further, we LPPO II have low propensity for resistance development, likely due to their rapid membrane-targeting mode of action. Finally, we reveal that LPPO II are not toxic to either eukaryotic cells or model animals when administered orally or topically. Collectively, these results suggest that LPPO II are highly promising compounds for development into pharmaceuticals.
• Lipophosphonoxins: New Modular Molecular Structures with Significant Antibacterial Properties
  作者：Dominik Rejman、Alžbeta Rabatinová、António R. Pombinho、Soňa Kovačková、Radek Pohl、Eva Zbornı́ková、Milan Kolář、Kateřina Bogdanová、Otakar Nyč、Hana Šanderová、Tomáš Látal、Petr Bartůněk、Libor Krásný

  DOI：10.1021/jm2009343

  日期：2011.11.24

  Novel compounds termed lipophosphonoxins were prepared using a simple and efficient synthetic approach. The general structure of lipophosphonoxins consists of four modules: (i) a nucleoside module, (ii) an iminosugar module, (iii) a hydrophobic module (lipophilic alkyl chain), and (iv) a phosphonate linker module that holds together modules i-iii. Lipophosphonoxins displayed significant antibacterial properties against a panel of Gram-positive species, including multiresistant strains. The minimum inhibitory concentration (MIC) values of the best inhibitors were in the 1-12 mu g/mL range, while their cytotoxic concentrations against human cell lines were significantly above this range. The modular nature of this artificial scaffold offers a large number of possibilities for further modifications/exploitation of these compounds.