3,4-di(oleyloxy)benzoic acid | 232264-32-3

• 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: 3,4-di(oleyloxy)benzoic acid
• 英文别名: 3,4-Bis(((Z)-octadec-9-en-1-yl)oxy)benzoic acid；3,4-bis[(Z)-octadec-9-enoxy]benzoic acid
• CAS: 232264-32-3
• 化学式: C₄₃H₇₄O₄
• 分子量: 655.058
• InChiKey: IPWLBEHHSJJJRH-CLFAGFIQSA-N

物化性质

• 沸点：
  727.0±60.0 °C(Predicted)
• 密度：
  0.937±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  17.4
• 重原子数：
  47
• 可旋转键数：
  35
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,4-di(oleyloxy)benzoic acid 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 N-[2-(2-aminoethyldisulfanyl)-ethyl]-3,4-di(oleyloxy)benzamide trifluoroacetate
  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 在 乙醇 、 三苯基膦 、 potassium hydroxide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 4.0h， 生成 3,4-di(oleyloxy)benzoic acid
  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

文献信息

• Efficient Synthesis and Cell-Transfection Properties of a New Multivalent Cationic Lipid for Nonviral Gene Delivery
  作者：Kai Ewert、Ayesha Ahmad、Heather M. Evans、Hans-Werner Schmidt、Cyrus R. Safinya

  DOI：10.1021/jm020233w

  日期：2002.11.1

  Lipid-mediated delivery of DNA into cells holds great promise both for gene therapy and basic research applications. This paper describes the efficient and facile synthesis and the characterization of a new multivalent cationic lipid with a double-branched headgroup structure for gene delivery applications. The synthetic scheme can be extended to give cationic lipids of different charge, spacer, or

  脂质介导的将DNA传递到细胞中对于基因治疗和基础研究应用都具有广阔的前景。本文介绍了一种高效，简便的合成方法，以及一种具有双分支头基结构的新型多价阳离子脂质的表征，可用于基因传递。可以扩展合成方案以产生具有不同电荷，间隔基或脂质链长度的阳离子脂质。阳离子脂质体（CLs）与DNA的自组装复合物的化学和物理性质表明了为什么多价阳离子脂质具有卓越的转染特性。脂质在完全质子化的状态下带有一个带有五个电荷的头基，该头基连接到基于3,4-二羟基苯甲酸的不饱和双链疏水部分上。由新的多价脂质和中性脂质1,2-二油酰基-sn-甘油磷脂酰胆碱（DOPC）组成的脂质体用于制备与DNA的复合物。通过光学显微镜和小角度X射线散射对这些复合物的结构进行研究，发现CL-DNA复合物的层状Lα（C）相夹在脂质双层之间的DNA分子。使用含有萤火虫荧光素酶报道基因的质粒DNA进行的实验表明，这些复合物可以有效地转染哺乳动物细胞。与一价阳离子脂质2
• Acid-sensitive PEG-removable nanoscale liposomes for delivery of doxorubicin in A549/ADR therapy
  作者：Hailiang Chen、Chenyu Liu、Simiao Yu、Hengjun Zhou、Farishta Shafiq、Weihong Qiao

  DOI：10.1039/d3nj01764h

  日期：——

  carrier modification. However, PEG modification impedes cellular uptake of drug carriers and intracellular release of drugs, a problem known as the “PEG dilemma” that limits its application. In this study, we designed and synthesized mPEG-NCH-DOB molecules with acid-sensitive hydrazone bonding for the responsive removal of PEG. Drug-loaded lipid PHDGX for doxorubicin (DOX) delivery was obtained by compounding

  聚乙二醇（PEG）可以赋予药物载体长循环性能，常用于药物载体修饰。然而，PEG修饰阻碍了细胞对药物载体的摄取和药物在细胞内的释放，这一问题被称为“PEG困境”，限制了其应用。在本研究中，我们设计并合成了具有酸敏感腙键合的 mPEG-N CH-DOB 分子，用于响应性去除 PEG。用于阿霉素（DOX）递送的载药脂质 PHDGX 是通过将 mPEG-N CH-DOB 与脂质 DOPG 复合而获得的，其具有长循环能力和酸敏感的 PEG 去除能力，可加速药物释放并增强细胞摄取。聚乙二醇-NCH-DOB在pH 5.0下24小时后断裂率可达到50%。细胞毒性试验和流式细胞术（FCM）结果表明，在低DOX浓度下，PHDGX比游离DOX更容易进入A549/ADR细胞，并具有更强的抗癌能力。通过共聚焦激光扫描显微镜（CLSM）研究，发现PHDGX在同一时间点比游离DOX更容易进入A549/ADR细胞核，这表
• 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.
• A Columnar Phase of Dendritic Lipid−Based Cationic Liposome−DNA Complexes for Gene Delivery:  Hexagonally Ordered Cylindrical Micelles Embedded in a DNA Honeycomb Lattice
  作者：Kai K. Ewert、Heather M. Evans、Alexandra Zidovska、Nathan F. Bouxsein、Ayesha Ahmad、Cyrus R. Safinya

  DOI：10.1021/ja055907h

  日期：2006.3.1

  Gene therapy holds great promise as a future approach to fighting disease and is explored in worldwide clinical trials. Cationic liposome (CL)-DNA complexes are a prevalent nonviral delivery vector, but their efficiency requires improvement and the understanding of their mechanism of action is incomplete. As part of our effort to investigate the structure-transfection efficiency relationships of self-assembled CL-DNA vectors, we have synthesized a new, highly charged (16+) multivalent cationic lipid, MVLBG2, with a dendritic headgroup. Our synthetic scheme allows facile variation of the headgroup charge and the spacer connecting hydrophobic and headgroup moieties as well as gram-scale synthesis. Complexes of DNA with mixtures of MVLBG2 and neutral 1,2-dioleoyl-sn-glycerophosphatidylcholine (DOPC) exhibit the well-known lamellar phase at 90 mol % DOPC. Starting at 20 mol % dendritic lipid, however, two novel nonlamellar phases are observed by synchrotron X-ray diffraction. The structure of one of these phases, present in a narrow range of composition around 25 mol % MVLBG2, has been solved. In this novel dual lattice structure, termed H-l(C), hexagonally arranged tubular lipid micelles are surrounded by DNA rods forming a three-dimensionally continuous substructure with honeycomb symmetry. Complexes in the H-l(C) phase efficiently transfect mouse and human cells in culture. Their transfection efficiency, as well as that of the lamellar complexes containing only 10 mol % dendritic lipid, reaches and surpasses that of commercially available, optimized DOTAP-based complexes. In particular, complexes containing MVLBG2 are significantly more transfectant over the entire composition range in mouse embryonic fibroblasts, a cell line empirically known to be hard to transfect.
• PEG-LIPID CONJUGATES FOR INCREASING THE SOLUBILITY OF DRUG COMPOUNDS
  申请人：Keller, Brian Charles

  公开号：EP2389156A1

  公开（公告）日：2011-11-30