(2R,3S,4S,5R,6R)-2-(acetoxymethyl)-6-(2-(2-(2-(3-(6-(((2-((2-hydroxyethyl)disulfaneyl)ethoxy)carbonyl)amino)-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propanamido)ethoxy)ethoxy)ethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate | 1353569-67-1

• 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,3S,4S,5R,6R)-2-(acetoxymethyl)-6-(2-(2-(2-(3-(6-(((2-((2-hydroxyethyl)disulfaneyl)ethoxy)carbonyl)amino)-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propanamido)ethoxy)ethoxy)ethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate
• CAS: 1353569-67-1
• 化学式: C₄₀H₅₁N₃O₁₈S₂
• 分子量: 925.986
• InChiKey: FKPYFPCRJLKTSC-UEAOGTJRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.0
• 重原子数：
  63.0
• 可旋转键数：
  25.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  267.16
• 氢给体数：
  3.0
• 氢受体数：
  20.0

反应信息

• 作为反应物：
  描述：

  (2R,3S,4S,5R,6R)-2-(acetoxymethyl)-6-(2-(2-(2-(3-(6-(((2-((2-hydroxyethyl)disulfaneyl)ethoxy)carbonyl)amino)-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propanamido)ethoxy)ethoxy)ethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate 在 sodium methylate 作用下， 以 甲醇 为溶剂， 以61%的产率得到2-(2-hydroxyethyldisulfanyl)ethyl N-[1,3-dioxo-2-[3-oxo-3-[2-[2-[2-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyethoxy]ethoxy]ethylamino]propyl]benzo[de]isoquinolin-6-yl]carbamate
  参考文献：
  名称：

  Hepatocyte-Targeting Single Galactose-Appended Naphthalimide: A Tool for Intracellular Thiol Imaging in Vivo

  摘要：

  We present the design, synthesis, spectroscopic properties, and biological evaluation of a single galactose-appended naphthalimide (1). Probe 1 is a multifunctional molecule that incorporates a thiol-specific cleavable disulfide bond, a masked phthalamide fluorophore, and a single galactose moiety as a hepatocyte-targeting unit. It constitutes a new type of targetable ligand for hepatic thiol imaging in living cells and animals. Confocal microscopic imaging experiments reveal that 1, but not the galactose-free control system 2, is preferentially taken up by HepG2 cells through galactose-targeted, ASGP-R-mediated endocytosis. Probe 1 displays a fluorescence emission feature at 540 nm that is induced by exposure to free endogenous thiols, most notably GSH. The liver-specificity of 1 was confirmed in vivo via use of a rat model. The potential utility of this probe in indicating pathogenic states and as a possible screening tool for agents that can manipulate oxidative stress was demonstrated in experiments wherein palmitate was used to induce lipotoxicity in HepG2 cells.

  DOI：

  10.1021/ja210065g
• 作为产物：
  描述：

  (2R,3S,4S,5R,6R)-2-(acetoxymethyl)-6-(2-(2-(2-(3-(6-amino-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propanamido)ethoxy)ethoxy)ethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 3.0h， 生成 (2R,3S,4S,5R,6R)-2-(acetoxymethyl)-6-(2-(2-(2-(3-(6-(((2-((2-hydroxyethyl)disulfaneyl)ethoxy)carbonyl)amino)-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propanamido)ethoxy)ethoxy)ethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate
  参考文献：
  名称：

  Hepatocyte-Targeting Single Galactose-Appended Naphthalimide: A Tool for Intracellular Thiol Imaging in Vivo

  摘要：

  We present the design, synthesis, spectroscopic properties, and biological evaluation of a single galactose-appended naphthalimide (1). Probe 1 is a multifunctional molecule that incorporates a thiol-specific cleavable disulfide bond, a masked phthalamide fluorophore, and a single galactose moiety as a hepatocyte-targeting unit. It constitutes a new type of targetable ligand for hepatic thiol imaging in living cells and animals. Confocal microscopic imaging experiments reveal that 1, but not the galactose-free control system 2, is preferentially taken up by HepG2 cells through galactose-targeted, ASGP-R-mediated endocytosis. Probe 1 displays a fluorescence emission feature at 540 nm that is induced by exposure to free endogenous thiols, most notably GSH. The liver-specificity of 1 was confirmed in vivo via use of a rat model. The potential utility of this probe in indicating pathogenic states and as a possible screening tool for agents that can manipulate oxidative stress was demonstrated in experiments wherein palmitate was used to induce lipotoxicity in HepG2 cells.

  DOI：

  10.1021/ja210065g