(2R)-2-amino-3-[[(2R)-2-amino-3-(octadecylamino)-3-oxopropyl]disulfanyl]-N-octadecylpropanamide | 1027517-79-8

• 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: (2R)-2-amino-3-[[(2R)-2-amino-3-(octadecylamino)-3-oxopropyl]disulfanyl]-N-octadecylpropanamide
• CAS: 1027517-79-8
• 化学式: C₄₂H₈₆N₄O₂S₂
• 分子量: 743.302
• InChiKey: OQFGDOTXVJMQMR-ZAQUEYBZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  15.5
• 重原子数：
  50
• 可旋转键数：
  41
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  161
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  9,14,18-tris(tert-butoxycarbonyl)-2,2-dimethyl-4-oxo-3-oxa-5,9,14,18-tetraazaicosan-20-oic acid 、 (2R)-2-amino-3-[[(2R)-2-amino-3-(octadecylamino)-3-oxopropyl]disulfanyl]-N-octadecylpropanamide 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 tert-butyl N-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]-N-[4-[(2-methylpropan-2-yl)oxycarbonyl-[3-[(2-methylpropan-2-yl)oxycarbonyl-[2-[[(2R)-3-[[(2R)-2-[[2-[(2-methylpropan-2-yl)oxycarbonyl-[3-[(2-methylpropan-2-yl)oxycarbonyl-[4-[(2-methylpropan-2-yl)oxycarbonyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]butyl]amino]propyl]amino]acetyl]amino]-3-(octadecylamino)-3-oxopropyl]disulfanyl]-1-(octadecylamino)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]propyl]amino]butyl]carbamate
  参考文献：
  名称：

  Reduction-Sensitive Lipopolyamines as a Novel Nonviral Gene Delivery System for Modulated Release of DNA with Improved Transgene Expression

  摘要：

  We have designed and synthesized original cationic lipids for modulated release of DNA from cationic lipid/DNA complexes. Our rationale was that modulated degradation of the lipids during or after penetration into the cell could improve the trafficking of DNA to the nucleus resulting in increased transgene expression. The new reduction-sensitive lipopolyamines (RSL) harbor a disulfide bridge within different positions in the backbone of the lipids as biosensitive function. A useful synthetic method was developed to obtain, with very good yields and reproducibility, unsymmetrical disulfide-bridged molecules, starting from symmetrical disulfides and thiols. The new lipopolyamines are good candidates as carriers of therapeutic genes for in vivo gene delivery. To optimize the transfection efficiency in these novel series, we have carried out structure-activity relationship studies by placing the disulfide bridge at different positions in the backbone of the cationic lipid and by systematic variation of lipid chain length. Results indicate that the transfection level can be modulated as a function of the location of the disulfide bridge in the molecule. We suggest that an early release of DNA. during or after penetration into the cell, probably promoted by reduction of a disulfide bridge placed between the polyamine and the lipid, implies a total loss of transfection efficiency. On the other hand, proper modulation of DNA release by inserting the disulfide bridge between one lipid chain and the rest of the molecule brings about increased transfection efficiency as compared to previously described nondegradable lipopolyamine analogues. Finally, preliminary physicochemical characterization of the complexes demonstrates that DNA release from complexes can be modulated as a function of the surrounding reducing conditions of the complexes and of the localization of the disulfide bridge within the lipopolyamine. Our results suggest that RSL is a promising new approach for gene delivery.

  DOI：

  10.1021/jm000284y
• 作为产物：
  描述：

  L-胱氨酸 在 N-甲基吗啉 、 三氟乙酸 、 sodium hydroxide 、 氯甲酸异丁酯 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 47.0h， 生成 (2R)-2-amino-3-[[(2R)-2-amino-3-(octadecylamino)-3-oxopropyl]disulfanyl]-N-octadecylpropanamide
  参考文献：
  名称：

  Cationic gemini lipids with cyclen headgroups: interaction with DNA and gene delivery abilities

  摘要：

  合成了十一种双子星阳离子脂质和一种单体对应物，并研究了它们作为非病毒基因载体的结构-活性关系。

  DOI：

  10.1039/c4ra05974c