4-(2-tert-butoxycarboxyethyl)-4-[3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)propionylamino]heptanedioic acid di-tert-butyl ester | 905858-79-9

• 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: 4-(2-tert-butoxycarboxyethyl)-4-[3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)propionylamino]heptanedioic acid di-tert-butyl ester
• 英文别名: di-tert-butyl 4-(2-(tert-butoxycarbonyl)ethyl)-4-(3-(1,3-dioxoisoindolin-2-yl)propanamido)heptanedioate；Ditert-butyl 4-[3-(1,3-dioxoisoindol-2-yl)propanoylamino]-4-[3-[(2-methylpropan-2-yl)oxy]-3-oxopropyl]heptanedioate
• CAS: 905858-79-9
• 化学式: C₃₃H₄₈N₂O₉
• 分子量: 616.752
• InChiKey: LTSFMXZXPDWWFQ-UHFFFAOYSA-N

物化性质

• 熔点：
  144-145 °C
• 沸点：
  707.3±60.0 °C(predicted)
• 密度：
  1.149±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  44
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  145
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-(2-tert-butoxycarboxyethyl)-4-[3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)propionylamino]heptanedioic acid di-tert-butyl ester 在 肼 作用下， 以 乙醇 、 水 为溶剂， 反应 3.0h， 以85%的产率得到di-tert-butyl 4-(2-(tert-butoxycarbonyl)ethyl)-4-(3-aminopropanamido)heptanedioate
  参考文献：
  名称：

  荧光3-羟基-4-吡啶酮六齿铁螯合剂：细胞内分布及其与抗分枝杆菌特性的关系

  摘要：

  摘要我们报告了荧光铁螯合剂的合成和表征（4），显示出可有效抑制鸟分枝杆菌的生长。在巨噬细胞中的合成，以及两种不成功的类似物的合成和表征，这些类似物的选择有利于鉴定负责抗菌活性的分子特性。研究了螯合剂在脂质体中的分配，并通过流式细胞术和共聚焦显微镜检查了这些化合物在巨噬细胞摄取，对铁超载/铁剥夺的反应性以及细胞内分布方面的作用。六齿螯合剂的合成基于四面体结构，三个二齿3-羟基-4-吡啶酮螯合单元通过酰胺键连接。该结构具有合成通用性，可以进一步添加官能团，例如荧光团。在这里，我们分析非功能化的六齿单元（3）和相应的若丹明B（4）和荧光素（5）标记的螯合剂。铁（III）的稳定常数被确定为3，其值记录 β  = 34.4和PFE 3+  = 29.8指示量值作为分枝杆菌铁载体的相同的顺序的铁的亲和力。在脂质体存在下的荧光性质表明，4与脂质相强烈相互作用，而5没有。这种不同的行为可以解释其共聚焦显微

  DOI：

  10.1007/s00775-010-0650-1
• 作为产物：
  描述：

  N-乙氧羰基邻苯二甲酰亚胺 在 sodium carbonate 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 4-(2-tert-butoxycarboxyethyl)-4-[3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)propionylamino]heptanedioic acid di-tert-butyl ester
  参考文献：
  名称：

  Iron Binding Dendrimers:  A Novel Approach for the Treatment of Haemochromatosis

  摘要：

  A range of iron binding dendrimers terminated with hexadentate ligands formed from hydroxypyridinone, hydroxypyranone, and catechol moieties have been synthesized in order to investigate their potential as clinically useful iron(III)-selective chelators capable of removing dietary iron from the gastrointestinal tract and preventing the development of iron overload typical of haemochromatosis and thalassaemia intermedia. The iron chelating abilities of these molecules have been characterized by MALDI-TOF mass spectrometry and UV spectrometry. Hydroxypyridinone-terminated dendrimers were found to possess a high affinity and selectivity for iron(III). A hydroxypyridinone-based dendrimer was demonstrated to be highly efficient at reducing the absorption of iron(III) in rat intestine. This family of dendrimers may find an application in the treatment of iron overload.

  DOI：

  10.1021/jm0600949

文献信息

• The selective quantification of iron by hexadentate fluorescent probes
  作者：Yong Min Ma、Robert C. Hider

  DOI：10.1016/j.bmc.2009.09.052

  日期：2009.12

  The synthesis of four hexadentate fluorescent probes is described, where the fluorescent moiety is based on either coumarin or fluorescein and the chelating moiety is based on either 3-hydroxypyridin-4-one or 3-hydroxypyran-4-one. The fluorescence is quenched when the probe chelating moieties bind iron. The probes were found to be selective for iron over other metals such as Cu, Zn, Ni, Mn and Co. The effect of Cu on fluorescence quenching can be eliminated in the presence of N, N, N', N'-tetrakis(2-pyridylmethyl)-ethylenediamine. Competition studies demonstrate that the exchange of iron between pyridinone-based probes and apotransferrin is very slow. The ability to scavenge iron from oligomeric iron(III) citrate complexes demonstrate that the pyridinone probes scavenges iron faster than deferiprone and desferrioxamine. The fluorescence intensity of the fluorescein-based probe is quantitatively related to the iron concentration with the limit of detection being 10(8) M. (C) 2009 Elsevier Ltd. All rights reserved.
• Fluorescent 3-hydroxy-4-pyridinone hexadentate iron chelators: intracellular distribution and the relevance to antimycobacterial properties
  作者：Ana Nunes、Maria Podinovskaia、Andreia Leite、Paula Gameiro、Tao Zhou、Yongmin Ma、Xiaole Kong、Ulrich E. Schaible、Robert C. Hider、Maria Rangel

  DOI：10.1007/s00775-010-0650-1

  日期：2010.8

  hexadentate unit (3) and the corresponding rhodamine B (4) and fluorescein (5) labelled chelators. The iron(III) stability constant was determined for 3 and the values log β = 34.4 and pFe3+ = 29.8 indicate an affinity for iron of the same order of magnitude as that of mycobacteria siderophores. Fluorescence properties in the presence of liposomes show that 4 strongly interacts with the lipid phase, whereas

  摘要我们报告了荧光铁螯合剂的合成和表征（4），显示出可有效抑制鸟分枝杆菌的生长。在巨噬细胞中的合成，以及两种不成功的类似物的合成和表征，这些类似物的选择有利于鉴定负责抗菌活性的分子特性。研究了螯合剂在脂质体中的分配，并通过流式细胞术和共聚焦显微镜检查了这些化合物在巨噬细胞摄取，对铁超载/铁剥夺的反应性以及细胞内分布方面的作用。六齿螯合剂的合成基于四面体结构，三个二齿3-羟基-4-吡啶酮螯合单元通过酰胺键连接。该结构具有合成通用性，可以进一步添加官能团，例如荧光团。在这里，我们分析非功能化的六齿单元（3）和相应的若丹明B（4）和荧光素（5）标记的螯合剂。铁（III）的稳定常数被确定为3，其值记录 β  = 34.4和PFE 3+  = 29.8指示量值作为分枝杆菌铁载体的相同的顺序的铁的亲和力。在脂质体存在下的荧光性质表明，4与脂质相强烈相互作用，而5没有。这种不同的行为可以解释其共聚焦显微
• Iron Binding Dendrimers:  A Novel Approach for the Treatment of Haemochromatosis
  作者：Tao Zhou、Hendrik Neubert、Ding Yong Liu、Zu Dong Liu、Yong Min Ma、Xiao Le Kong、Wei Luo、Sykes Mark、Robert C. Hider

  DOI：10.1021/jm0600949

  日期：2006.7.1

  A range of iron binding dendrimers terminated with hexadentate ligands formed from hydroxypyridinone, hydroxypyranone, and catechol moieties have been synthesized in order to investigate their potential as clinically useful iron(III)-selective chelators capable of removing dietary iron from the gastrointestinal tract and preventing the development of iron overload typical of haemochromatosis and thalassaemia intermedia. The iron chelating abilities of these molecules have been characterized by MALDI-TOF mass spectrometry and UV spectrometry. Hydroxypyridinone-terminated dendrimers were found to possess a high affinity and selectivity for iron(III). A hydroxypyridinone-based dendrimer was demonstrated to be highly efficient at reducing the absorption of iron(III) in rat intestine. This family of dendrimers may find an application in the treatment of iron overload.