5-[[5-[(5-carboxy-3-ethyl-4-methyl-1H-pyrrol-2-yl)methyl]-1H-pyrrol-2-yl]methyl]-4-ethyl-3-methyl-1H-pyrrole-2-carboxylic acid | 500003-14-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 5-[[5-[(5-carboxy-3-ethyl-4-methyl-1H-pyrrol-2-yl)methyl]-1H-pyrrol-2-yl]methyl]-4-ethyl-3-methyl-1H-pyrrole-2-carboxylic acid
• CAS: 500003-14-5
• 化学式: C₂₂H₂₇N₃O₄
• 分子量: 397.474
• InChiKey: YFZUYTOEBFBLGU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  122
• 氢给体数：
  5
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-[[5-[(5-carboxy-3-ethyl-4-methyl-1H-pyrrol-2-yl)methyl]-1H-pyrrol-2-yl]methyl]-4-ethyl-3-methyl-1H-pyrrole-2-carboxylic acid 在 zinc diacetate 、 sodium acetate 、 三氟乙酸 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 50.17h， 生成
  参考文献：
  名称：

  Metallation of pentaphyrin with Lu(III) dramatically increases reactive-oxygen species production and cell phototoxicity

  摘要：

  Photodynamic therapy (PDT) is an emerging cancer treatment modality based on the excitation of a nontoxic photosensitizer with harmless visible light to produce reactive-oxygen species (ROS) that induce apoptosis and/or necrosis in cancer cells. As the efficacy of this therapy strongly depends of the nature of the photosensitizer, there is a great interest to develop new photoactive molecules. Here we report for the first time the synthesis, characterization and bioactivity of metal complexes between the non-aromatic expanded porphyrin, namely 20-[[4'-(Trimethylsilyl)ethoxycarbonyl]phenyl-2,13-dimethyl-3,12-diethyl-[24] iso-pentaphyrin (PCRed) and Zn(II) [Zn(II)-PCRed] or Lu(III) [Lu(III)-PCRed]. The complexation of these two diamagnetic heavy metal ions to PCRed improved the properties of the free photosensitizer as a PDT drug. We discovered that the 1:1 complex between PCRed and Lu(III) significantly increases the cellular uptake, ROS production and antiproliferative capacity in four cancer cell lines. Our study shows that metal complexation is a useful strategy to potentiate iso-pentaphyrin as a PDT drug. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.12.007
• 作为产物：
  描述：

  2,5-bis(5-benzyloxycarbonyl-3-ethyl-4-methyl-2-pyrrolylmethyl)pyrrole 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 20.0 ℃ 、275.79 kPa 条件下， 反应 16.0h， 以98%的产率得到5-[[5-[(5-carboxy-3-ethyl-4-methyl-1H-pyrrol-2-yl)methyl]-1H-pyrrol-2-yl]methyl]-4-ethyl-3-methyl-1H-pyrrole-2-carboxylic acid
  参考文献：
  名称：

  氧苯并卟啉，氧并卟啉，苯甲碳卟啉及其23-氧杂和23-硫杂类似物：钯（II）有机金属衍生物的合成，光谱表征，金属化和结构表征†

  摘要：

  使用MacDonald缩合反应中的“ 3 +1”变体合成了一系列九种卟啉类似物。使用常规方法制备具有中心未取代的吡咯，呋喃或噻吩环的三吡喃型体系，并在其中将它们与茚-1,3-二甲醛，5-甲酰基水杨醛或3-羟基-2,6-吡啶二甲醛缩合。存在TFA分别生成苯并咔巴，氧苯甲酰和氧焦卟啉。含呋喃的类似物被证明是高度碱性的，只能分离为相应的盐酸盐。所有九个类似物系统都显示出类似卟啉的UV-vis光谱，在400 nm附近有一个或两个Soret吸收，并在较长的波长处出现了一系列较弱的谱带。这些系统还通过质子NMR光谱显示出大的变径环电流，与真正的卟啉相当。在痕量的TFA存在下，苯并碳卟啉12个形成单阳离子，并在50％TFA中生成C质子化的指示。尽管在5％的Et 3 N-氯仿中生成了游离碱，但23-氧杂碳卟啉14在氯仿中产生了单阳离子。在50％TFA-CHCl 3中，14提供了单质子化和双质子化物质的混合

  DOI：

  10.1021/jo040180l

文献信息

• Oxybenziporphyrins, Oxypyriporphyrins, Benzocarbaporphyrins, and Their 23-Oxa and 23-Thia Analogues:  Synthesis, Spectroscopic Characterization, Metalation, and Structural Characterization of a Palladium(II) Organometallic Derivative
  作者：Dachun Liu、Gregory M. Ferrence、Timothy D. Lash

  DOI：10.1021/jo040180l

  日期：2004.9.1

  respectively. The furan-containing analogues proved to be highly basic and could only be isolated as the corresponding hydrochloride salts. All nine analogue systems showed porphyrin-like UV−vis spectra with one or two Soret absorptions near 400 nm and a series of weaker bands at longer wavelengths. These systems also showed large diatropic ring currents by proton NMR spectroscopy that were comparable to true

  使用MacDonald缩合反应中的“ 3 +1”变体合成了一系列九种卟啉类似物。使用常规方法制备具有中心未取代的吡咯，呋喃或噻吩环的三吡喃型体系，并在其中将它们与茚-1,3-二甲醛，5-甲酰基水杨醛或3-羟基-2,6-吡啶二甲醛缩合。存在TFA分别生成苯并咔巴，氧苯甲酰和氧焦卟啉。含呋喃的类似物被证明是高度碱性的，只能分离为相应的盐酸盐。所有九个类似物系统都显示出类似卟啉的UV-vis光谱，在400 nm附近有一个或两个Soret吸收，并在较长的波长处出现了一系列较弱的谱带。这些系统还通过质子NMR光谱显示出大的变径环电流，与真正的卟啉相当。在痕量的TFA存在下，苯并碳卟啉12个形成单阳离子，并在50％TFA中生成C质子化的指示。尽管在5％的Et 3 N-氯仿中生成了游离碱，但23-氧杂碳卟啉14在氯仿中产生了单阳离子。在50％TFA-CHCl 3中，14提供了单质子化和双质子化物质的混合
• Synthesis, spectroscopy and metallation of mixed carbaporphyrinoid systems
  作者：Dachun Liu、Timothy D. Lash

  DOI：10.1039/b206276n

  日期：——

  Modified tripyrranes incorporating furan and thiophene rings were found to condense with benzene, pyridine and indene dialdehydes to give a series of novel porphyrin analogues, including thia- and oxa-carbaporphyrins; the latter readily forms nickel(II) and palladium(II) organometallic complexes.

  发现结合了呋喃和噻吩环的改性三吡喃与苯，吡啶和茚二醛缩合，生成了一系列新颖的卟啉类似物，包括噻吩和氧杂咔啉。后者容易形成镍（II）和钯（II）有机金属配合物。
• β-Cyano meso-unsubstituted porphyrins for intramolecular charge transfer
  作者：Olivier Siri、Kevin M. Smith

  DOI：10.1016/s0040-4039(03)01458-8

  日期：2003.8

  b-Cyano meso-unsubstituted porphyrin 10, synthesized via a '3+1' condensation using a bromotripyrrane, shows an effective charge transfer interaction across the porphyrin between electron-acceptor and -donor groups in beta-positions. (C) 2003 Elsevier Ltd. All rights reserved.
• 6-Oxopyriphlorins
  作者：Alexandra M. Young、Timothy D. Lash

  DOI：10.1039/c3ob41506f

  日期：——

  in the presence of trifluoroacetic acid, followed by oxidation of a pyriphlorin intermediate with silver(I) acetate, gave 6-oxopyriphlorins in moderate to good yields. The oxophlorin analogues were nonaromatic porphyrinoids that gave bright green colored solutions. Protonation with TFA afforded species that were attributed to mono- and dicationic structures. The proton NMR spectra in TFA–CDCl3 showed

  在三氟乙酸的存在下，2,6-吡啶二甲醛与一系列三吡喃反应，然后用乙酸银（I）氧化吡ip啉中间体，以中等至良好的收率得到6-氧-啶酮。氧卟啉类似物是非芳族卟啉类化合物，可产生亮绿色的溶液。用TFA质子化可得到归因于单和双键结构的物种。TFA–CDCl3中的质子NMR光谱显示低场向中质子转移，高场向内部NH共振转移，表明存在弱的变径性指示性物质。6-氧吡咯啉与DMF中的乙酸镍（II）或乙腈中的乙酸钯（II）反应，得到相应的金属衍生物。
• Metallation of pentaphyrin with Lu(III) dramatically increases reactive-oxygen species production and cell phototoxicity
  作者：Maurizio Ballico、Valentina Rapozzi、Luigi E. Xodo、Clara Comuzzi

  DOI：10.1016/j.ejmech.2010.12.007

  日期：2011.2

  Photodynamic therapy (PDT) is an emerging cancer treatment modality based on the excitation of a nontoxic photosensitizer with harmless visible light to produce reactive-oxygen species (ROS) that induce apoptosis and/or necrosis in cancer cells. As the efficacy of this therapy strongly depends of the nature of the photosensitizer, there is a great interest to develop new photoactive molecules. Here we report for the first time the synthesis, characterization and bioactivity of metal complexes between the non-aromatic expanded porphyrin, namely 20-[[4'-(Trimethylsilyl)ethoxycarbonyl]phenyl-2,13-dimethyl-3,12-diethyl-[24] iso-pentaphyrin (PCRed) and Zn(II) [Zn(II)-PCRed] or Lu(III) [Lu(III)-PCRed]. The complexation of these two diamagnetic heavy metal ions to PCRed improved the properties of the free photosensitizer as a PDT drug. We discovered that the 1:1 complex between PCRed and Lu(III) significantly increases the cellular uptake, ROS production and antiproliferative capacity in four cancer cell lines. Our study shows that metal complexation is a useful strategy to potentiate iso-pentaphyrin as a PDT drug. (C) 2010 Elsevier Masson SAS. All rights reserved.