N-2-[N'-(Nα-benzyloxycarbonyl-Nε-t-butyloxycarbonyl-L-Lysyl)]aminoethyl-N,N-di-n-tetradecylamine | 678975-64-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-2-[N'-(Nα-benzyloxycarbonyl-Nε-t-butyloxycarbonyl-L-Lysyl)]aminoethyl-N,N-di-n-tetradecylamine
• 英文别名: N-2-[N'-(N^α-benzyloxycarbonyl-N^ε-t-butyloxycarbonyl-L-Lysyl)]aminoethyl-N,N-di-n-tetradecylamine；N-2-[N'-(Nε-BOC-Nα-benzyloxycarbonyl-L-lysinyl)]aminoethyl-N,N-di-n-tetradecylamine
• CAS: 678975-64-9
• 化学式: C₄₉H₉₀N₄O₅
• 分子量: 815.277
• InChiKey: UZHLEKGJKRMOLO-GWHBCOKCSA-N

物化性质

• 沸点：
  866.9±65.0 °C(Predicted)
• 密度：
  0.973±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  12.8
• 重原子数：
  58.0
• 可旋转键数：
  38.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  109.0
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N-2-[N'-(Nα-benzyloxycarbonyl-Nε-t-butyloxycarbonyl-L-Lysyl)]aminoethyl-N,N-di-n-tetradecylamine 在 palladium on activated charcoal N-羟基丁二酰亚胺 、 ammonium formate 、 溶剂黄146 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.5h， 生成 N-2-[N'-(N^ε-tert-butyloxycarbonyl-L-Lys-N^ε-tert-butyloxycarbonyl-L-Lys)]aminoethyl-N,N-di-n-tetradecylamine
  参考文献：
  名称：

  Design, Syntheses and In Vitro Gene Delivery Efficacies of Novel Mono-, Di- and Trilysinated Cationic Lipids:  A Structure−Activity Investigation

  摘要：

  Structure-activity investigation including design, syntheses, and evaluation of relative in vitro gene delivery efficacies of a novel series of cationic amphiphiles (1-10) containing mono-, di-, and trilysine headgroups are described in CHO, COS-1, and HepG2 cells. Several interesting and rather unexpected transfection profiles were observed. In general, lipid 1 with the myristyl tail used in combination with DOPE as colipid exhibited superior transfection properties compared to (a) the monolysinated analogues with longer hydrocarbon tails (lipids 2-4), (b) the dilysine (lipids 5-7) and the trilysine headgroup analogues (lipids 8-10), and (c) commercially available LipofectAmine with multiple positive charges in its polar region. As a preliminary estimate of the relative DNA-compacting efficacies of these new lysinated cationic lipids, the hydrodynamic diameters of representative lipoplexes were measured using dynamic laser light scattering technique. Our lipoplex size data are consistent with the notion that covalent grafting of an increasing number of positively charged functional groups in the headgroup region of cationic lipids need not necessarily result in more compacted lipoplexes. Both gel retardation and DNase I sensitivity assays indicated similar lipid/DNA binding interactions for all the novel mono-, di-, and trilysinated cationic lipids. MTT-assay-based cell viability results clearly demonstrate that the overall lower transfection properties of trilysine analogues (8-10) compared to their mono- (1-4) and dilysinated (5-7) counterparts are unlikely to originate from differential toxicity related effects. Taken together, the present findings support the notion that caution needs to be exercised in ensuring enhanced gene delivery efficacies of cationic lipids through covalent grafting of multiple lysine functionalities in the headgroup region.

  DOI：

  10.1021/jm030541+
• 作为产物：
  描述：

  Nε-Boc-Nα-Cbz-L-赖氨酸 、 N1,N1-ditetradecylethane-1,2-diamine 在 4-二甲氨基吡啶 N-羟基丁二酰亚胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 以58%的产率得到N-2-[N'-(Nα-benzyloxycarbonyl-Nε-t-butyloxycarbonyl-L-Lysyl)]aminoethyl-N,N-di-n-tetradecylamine
  参考文献：
  名称：

  [EN] METHODS AND COMPOSITIONS COMPRISING NOVEL CATIONIC LIPIDS
  [FR] PROCÉDÉS ET COMPOSITIONS COMPRENANT DE NOUVEAUX LIPIDES CATIONIQUES

  摘要：

  本文提供了新型阳离子脂质、含有这些阳离子脂质的组合物，以及使用这些阳离子脂质的方法。在一些声明中，这些阳离子脂质具有细胞毒活性，可以单独使用或与细胞毒生物活性化合物结合使用以杀死细胞。在其中一些声明中，这些阳离子脂质增强了细胞毒生物活性化合物的细胞毒活性。提供了治疗患有疾病或不良状况的受试者的方法，其中该方法包括向受试者施用含有新型阳离子脂质的传递系统。该发明还提供了制备包含该发明的新型阳离子脂质的传递系统的方法。

  公开号：

  WO2009142892A1