N-[2-(2-aminoethyldisulfanyl)-ethyl]-3,4-di(oleyloxy)benzamide trifluoroacetate | 1323443-53-3

• 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: N-[2-(2-aminoethyldisulfanyl)-ethyl]-3,4-di(oleyloxy)benzamide trifluoroacetate
• 英文别名: N-[2-(2-aminoethyldisulfanyl)ethyl]-3,4-bis[(Z)-octadec-9-enoxy]benzamide;2,2,2-trifluoroacetic acid
• CAS: 1323443-53-3
• 化学式: C₂HF₃O₂*C₄₇H₈₄N₂O₃S₂
• 分子量: 903.352
• InChiKey: OXRAOFWGQHFUEI-AWLASTDMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  15.22
• 重原子数：
  61
• 可旋转键数：
  41
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  162
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (S)-2-(tert-butoxycarbonyl(3-(tert-butoxycarbonylamino)propyl)amino)-5-(tert-butoxycarbonylamino)pentanoic acid 、 N-[2-(2-aminoethyldisulfanyl)-ethyl]-3,4-di(oleyloxy)benzamide trifluoroacetate 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， 以72%的产率得到{(S)-1-[2-(2-{(3,4-di(oleyloxy)benzoyl)amino}-ethyldisulfanyl)-ethylcarbamoyl]-4-tert-butoxycarbonylamino-butyl}-(3-tert-butoxycarbonylamino-propyl)-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 在 乙醇 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 三苯基膦 、 potassium hydroxide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 22.0h， 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