tert-butyl(11S,14S)-11-(3-tert-butoxy-3-oxopropyl)-5-(3β-cholest-5-en-3-yl)-14-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-2,2-dimethyl-4,10,13-trioxo-3-oxa-5,9,12-triazaheptadecan-17-oate | 1039089-37-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: tert-butyl(11S,14S)-11-(3-tert-butoxy-3-oxopropyl)-5-(3β-cholest-5-en-3-yl)-14-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-2,2-dimethyl-4,10,13-trioxo-3-oxa-5,9,12-triazaheptadecan-17-oate
• 英文别名: tert-butyl (4S)-5-[3-[[(3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]propylamino]-4-[[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoyl]amino]-5-oxopentanoate
• CAS: 1039089-37-6
• 化学式: C₆₈H₁₀₂N₄O₁₀
• 分子量: 1135.58
• InChiKey: DEEOHPGOMDWQGG-CESOXGOCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  14.4
• 重原子数：
  82
• 可旋转键数：
  29
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  179
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  tert-butyl(11S,14S)-11-(3-tert-butoxy-3-oxopropyl)-5-(3β-cholest-5-en-3-yl)-14-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-2,2-dimethyl-4,10,13-trioxo-3-oxa-5,9,12-triazaheptadecan-17-oate 在 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 11-Fmoc-deprotected
  参考文献：
  名称：

  Selective Disruption of Early/Recycling Endosomes: Release of Disulfide-Linked Cargo Mediated by a N-Alkyl-3β-Cholesterylamine-Capped Peptide

  摘要：

  The use of endocytic uptake pathways to deliver poorly permeable molecules into mammalian cells is often plagued by entrapment and degradation of material in late endosomes and lysosomes. As a strategy to prevent the exposure of cargo to these highly hydrolytic membrane-sealed compartments, we synthesized derivatives of the membrane anchor N-alkyl-3 beta-cholesterylamine that selectively target linked compounds to less hydrolytic early/recycling endosomes. By targeting a pH-dependent membrane-lytic dodecapeptide and dislufide-linked flurophore to these compartments in Chinese hamster ovary cells or Jurkat lymphocytes, membranes of early-recycling endosomes were selectively disrupted, resulting in cleavage of the disulphide and escape of the fluorophore into cytosol and nucleus with low toxicity. The ability os appropriately designed N-alkyl-3 beta-cholesterylamines to deliver cargo into and release dislufide-linked cargo from relatively nonhydrolytic early/recycling endosomes may be useful for the delivery of a variety of sensitive molecules into living mammalian cells.

  DOI：

  10.1021/ja803380a
• 作为产物：
  描述：

  Fmoc-O-叔丁基-L-谷氨酸 、 在 1-羟基苯并三唑 、 1,2-二氯乙烷 作用下， 以 二氯甲烷 为溶剂， 反应 12.5h， 以172 mg的产率得到tert-butyl(11S,14S)-11-(3-tert-butoxy-3-oxopropyl)-5-(3β-cholest-5-en-3-yl)-14-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-2,2-dimethyl-4,10,13-trioxo-3-oxa-5,9,12-triazaheptadecan-17-oate
  参考文献：
  名称：

  Selective Disruption of Early/Recycling Endosomes: Release of Disulfide-Linked Cargo Mediated by a N-Alkyl-3β-Cholesterylamine-Capped Peptide

  摘要：

  The use of endocytic uptake pathways to deliver poorly permeable molecules into mammalian cells is often plagued by entrapment and degradation of material in late endosomes and lysosomes. As a strategy to prevent the exposure of cargo to these highly hydrolytic membrane-sealed compartments, we synthesized derivatives of the membrane anchor N-alkyl-3 beta-cholesterylamine that selectively target linked compounds to less hydrolytic early/recycling endosomes. By targeting a pH-dependent membrane-lytic dodecapeptide and dislufide-linked flurophore to these compartments in Chinese hamster ovary cells or Jurkat lymphocytes, membranes of early-recycling endosomes were selectively disrupted, resulting in cleavage of the disulphide and escape of the fluorophore into cytosol and nucleus with low toxicity. The ability os appropriately designed N-alkyl-3 beta-cholesterylamines to deliver cargo into and release dislufide-linked cargo from relatively nonhydrolytic early/recycling endosomes may be useful for the delivery of a variety of sensitive molecules into living mammalian cells.

  DOI：

  10.1021/ja803380a