Ethyl 3,4-di(oleyloxy)benzoate | 926652-62-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Ethyl 3,4-di(oleyloxy)benzoate
• 英文别名: ethyl 3,4-bis[(Z)-octadec-9-enoxy]benzoate
• CAS: 926652-62-2
• 化学式: C₄₅H₇₈O₄
• 分子量: 683.112
• InChiKey: RAERSYHPSRJMPV-WRBBJXAJSA-N

物化性质

• 沸点：
  721.4±60.0 °C(Predicted)
• 密度：
  0.922±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  17.9
• 重原子数：
  49
• 可旋转键数：
  37
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Ethyl 3,4-di(oleyloxy)benzoate 在 乙醇 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 22.0h， 生成 [2-(2-{[3,4-di(oleyloxy)benzoyl]amino}-ethyldisulfanyl)ethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and characterization of degradable multivalent cationic lipids with disulfide-bond spacers for gene delivery

  摘要：

  Gene therapy provides powerful new approaches to curing a large variety of diseases, which are being explored in ongoing worldwide clinical trials. To overcome the limitations of viral gene delivery systems, synthetic nonviral vectors such as cationic liposomes (CLs) are desirable. However, improvements of their efficiency at reduced toxicity and a better understanding of their mechanism of action are required. We present the efficient synthesis of a series of degradable multivalent cationic lipids (CMVLn, n=2 to 5) containing a disulfide bond spacer between headgroup and lipophilic tails. This spacer is designed to be cleaved in the reducing milieu of the cytoplasm and thus decrease lipid toxicity. Small angle X-ray scattering demonstrates that the initially formed lamellar phase of CMVLn-DNA complexes completely disappears when reducing agents such as DTT or the biologically relevant reducing peptide glutathione are added to mimic the intracellular milieu. The CMVLs (n=3 to 5) exhibit reduced cytotoxicity and transfect mammalian cells with efficiencies comparable to those of highly efficient non-degradable analogs and benchmark commercial reagents such as Lipofectamine 2000. Thus, our results demonstrate that degradable disulfide spacers may be used to reduce the cytotoxicity of synthetic nonviral gene delivery carriers without compromising their transfection efficiency. (C) 2011 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.bbamem.2011.04.020
• 作为产物：
  描述：

  油醇 、 3,4-二羟基苯甲酸乙酯 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 生成 Ethyl 3,4-di(oleyloxy)benzoate
  参考文献：
  名称：

  Synthesis and characterization of degradable multivalent cationic lipids with disulfide-bond spacers for gene delivery

  摘要：

  Gene therapy provides powerful new approaches to curing a large variety of diseases, which are being explored in ongoing worldwide clinical trials. To overcome the limitations of viral gene delivery systems, synthetic nonviral vectors such as cationic liposomes (CLs) are desirable. However, improvements of their efficiency at reduced toxicity and a better understanding of their mechanism of action are required. We present the efficient synthesis of a series of degradable multivalent cationic lipids (CMVLn, n=2 to 5) containing a disulfide bond spacer between headgroup and lipophilic tails. This spacer is designed to be cleaved in the reducing milieu of the cytoplasm and thus decrease lipid toxicity. Small angle X-ray scattering demonstrates that the initially formed lamellar phase of CMVLn-DNA complexes completely disappears when reducing agents such as DTT or the biologically relevant reducing peptide glutathione are added to mimic the intracellular milieu. The CMVLs (n=3 to 5) exhibit reduced cytotoxicity and transfect mammalian cells with efficiencies comparable to those of highly efficient non-degradable analogs and benchmark commercial reagents such as Lipofectamine 2000. Thus, our results demonstrate that degradable disulfide spacers may be used to reduce the cytotoxicity of synthetic nonviral gene delivery carriers without compromising their transfection efficiency. (C) 2011 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.bbamem.2011.04.020
• 作为试剂：
  描述：

  1-溴-顺-9-十八碳烯 、 3,4-二羟基苯甲酸乙酯 、 potassium carbonate 、 碘化钾 、 氢氧化钾 、 盐酸 在 氮气 、 Ethyl 3,4-di(oleyloxy)benzoate 、 乙醇 、 3,4-Bis-octadec-9-enyloxy-benzoic acid 、 水 、 crude acid 作用下， 以 环己酮 、 铝 、 水 为溶剂， 反应 22.0h， 以to give the product 8c as a white solid (1.14 g, 70%)的产率得到3,4-Bis-octadec-9-enyloxy-benzoic acid
  参考文献：
  名称：

  Lipophilic polyamines providing enhanced intracellular delivery of agents by a polyamine transport system

  摘要：

  合成了具有运输到具有活性多胺转运系统的细胞的能力的聚胺阳离子脂质。因此，这些脂质可以与各种药剂结合，并作为向细胞运输药剂的载体，利用细胞自身的多胺转运系统。将药剂与从化合物25、26、27、28及其药学上可接受的盐和其组合物中选择的多胺阳离子脂质关联，并与细胞接触的方法可将药剂传递到细胞中。

  公开号：

  US07910363B1

文献信息

• Synthesis and Transfection Efficiencies of New Lipophilic Polyamines
  作者：Richard Andrew Gardner、Mattias Belting、Katrin Svensson、Phanstiel

  DOI：10.1021/jm0607101

  日期：2007.1.1

  A homologous series of lipophilic polyamines was synthesized and evaluated for DNA delivery and transfection efficiency. The series contained 1,4-butanediamine, 1,8-octanediamine, 2-[2-(2-amino-ethoxy)-ethoxy]-ethylamine, homospermidine, and homospermine covalently attached via their N-1 terminus to a 3,4-bis(oleyloxy)-benzyl motif. In addition, homospermidine and homospermine were also attached via amide linkers. The homospermidine derivatives (i.e., benzyl tether 25 and benzamide tether 27) showed a 3-fold and 4-fold respective enhancement in delivery of AlexaFluor-488-labeled DNA over the butanediamine analogue 22. Homospermine derivative 26 was shown to inhibit C-14-spermine uptake (IC50 similar to 10 mu M), which implied that 26 is able to compete effectively for polyamine recognition sites on the cell surface. This study demonstrated that the number and position of the positive charges along the polyamine scaffold plays a key role in DNA delivery and in determining the transfection efficiency.
• US7910363B1
  申请人：——

  公开号：US7910363B1

  公开（公告）日：2011-03-22
• Synthesis and characterization of degradable multivalent cationic lipids with disulfide-bond spacers for gene delivery
  作者：Rahau S. Shirazi、Kai K. Ewert、Cecilia Leal、Ramsey N. Majzoub、Nathan F. Bouxsein、Cyrus R. Safinya

  DOI：10.1016/j.bbamem.2011.04.020

  日期：2011.9

  Gene therapy provides powerful new approaches to curing a large variety of diseases, which are being explored in ongoing worldwide clinical trials. To overcome the limitations of viral gene delivery systems, synthetic nonviral vectors such as cationic liposomes (CLs) are desirable. However, improvements of their efficiency at reduced toxicity and a better understanding of their mechanism of action are required. We present the efficient synthesis of a series of degradable multivalent cationic lipids (CMVLn, n=2 to 5) containing a disulfide bond spacer between headgroup and lipophilic tails. This spacer is designed to be cleaved in the reducing milieu of the cytoplasm and thus decrease lipid toxicity. Small angle X-ray scattering demonstrates that the initially formed lamellar phase of CMVLn-DNA complexes completely disappears when reducing agents such as DTT or the biologically relevant reducing peptide glutathione are added to mimic the intracellular milieu. The CMVLs (n=3 to 5) exhibit reduced cytotoxicity and transfect mammalian cells with efficiencies comparable to those of highly efficient non-degradable analogs and benchmark commercial reagents such as Lipofectamine 2000. Thus, our results demonstrate that degradable disulfide spacers may be used to reduce the cytotoxicity of synthetic nonviral gene delivery carriers without compromising their transfection efficiency. (C) 2011 Elsevier B.V. All rights reserved.
• Lipophilic polyamines providing enhanced intracellular delivery of agents by a polyamine transport system
  申请人：University of Central Florida Research Foundation, Inc.

  公开号：US07910363B1

  公开（公告）日：2011-03-22

  Polyamine cationic lipids have been synthesized that have the ability to be transported into cells having an active polyamine transport system. Accordingly, these lipids may be conjugated with various agents and, thereby, act as vectors for transporting the agent into the cell aided by the cell's own polyamine transport system. A method of delivering an agent into a cell includes associating the agent with a polyamine cationic lipid selected from compounds 25, 26, 27, 28, their pharmaceutically acceptable salts and combinations thereof and contacting the cell therewith.

  合成了具有运输到具有活性多胺转运系统的细胞的能力的聚胺阳离子脂质。因此，这些脂质可以与各种药剂结合，并作为向细胞运输药剂的载体，利用细胞自身的多胺转运系统。将药剂与从化合物25、26、27、28及其药学上可接受的盐和其组合物中选择的多胺阳离子脂质关联，并与细胞接触的方法可将药剂传递到细胞中。