3,3',5,5'-tetrakis(ethoxycarbonyl)-4,4'-bis(methoxyethyl)-2,2'-bipyrrole | 147008-81-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 3,3',5,5'-tetrakis(ethoxycarbonyl)-4,4'-bis(methoxyethyl)-2,2'-bipyrrole
• 英文别名: tetraethyl 4,4'-di(2-methoxyethyl)-2,2'-bipyrrole-3,3',5,5'-tetracarboxylate；diethyl 5-[3,5-bis(ethoxycarbonyl)-4-(2-methoxyethyl)-1H-pyrrol-2-yl]-3-(2-methoxyethyl)-1H-pyrrole-2,4-dicarboxylate
• CAS: 147008-81-9
• 化学式: C₂₆H₃₆N₂O₁₀
• 分子量: 536.579
• InChiKey: HFLYUQNJUUGFGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  38
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  155
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  3,3',5,5'-tetrakis(ethoxycarbonyl)-4,4'-bis(methoxyethyl)-2,2'-bipyrrole 在 ammonium hydroxide 、 sodium hydroxide 、 氧气 、 四氯化钛 、 copper(l) chloride 、 锌 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 230.0 ℃ 、26.66 Pa 条件下， 反应 42.53h， 生成 2,7,12,17-tetra-n-propyl-porphycene
  参考文献：
  名称：

  Photodynamic Antitumor Agents: .beta.-Methoxyethyl Groups Give Access to Functionalized Porphycenes and Enhance Cellular Uptake and Activity

  摘要：

  Porphycene photosensitizers bearing two or four methoxyethyl side chains were synthesized in nine steps from commercially available starting materials. Ether cleavage led to (hydroxyethyl)- and (bromoethyl)porphycenes that were converted to vinyl and benzo derivatives. Five of the side chain-functionalized porphycenes were biologically studied in comparison with two tetra-n-propylporphycenes. Porphycenes were incorporated in small unilamellar liposomes and incubated with cultivated SSK2 murine fibrosarcoma cells. Cellular uptake and phototoxicity 24 h after 5 J/cm(2) laser light treatment were determined. The porphycenes tested were between 17 and 220 times more photodynamically active than the currently clinically used sensitizer Photofrin, although extinction coefficients of the porphycenes' irradiated bands are only approximately 10-fold higher. The LD(50) concentration for SSK2 cells in the incubation medium was as low as (8.5 +/- 2.8) x 10(-9) M for tetrakis(methoxyethyl)porphycene. Two methoxy or hydroxy groups enhanced cellular uptake, three or four methoxy groups both enhanced and accelerated cellular uptake of tetraalkylporphycenes. Half-life times of the uptake processes varied between (0.14 +/- 0.04) and (14 +/- 4) h and cellular saturation levels between (1.2 +/- 0.2) and (26 +/- 3) pmol/10(5) cells. When individual uptake rates were accounted for, all porphycenes had a similar ''cellular'' phototoxicity, pointing toward a common mechanism of action. Evidence is presented for the assumption that cell membranes are the primary targets of the tested porphycenes and that membrane solubility may play a critical role in their photodynamic efficiency. The results show that nonionic polar side chain functionalities can strongly enhance cellular uptake and antitumor activity of lipophilic porphyrinoids and thus that the known lipophilicity/activity relationship can be reversed for very hydrophobic sensitizers.

  DOI：

  10.1021/jm00043a019
• 作为产物：
  描述：

  5-甲氧基-3-羰基-戊酸乙酯 在 磺酰氯 、 水 、 溴 、 碘 、 sodium acetate 、 乙酸酐 、 铜 、 碳酸氢钠 、 溶剂黄146 、 potassium iodide 、 锌 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 25.0h， 生成 3,3',5,5'-tetrakis(ethoxycarbonyl)-4,4'-bis(methoxyethyl)-2,2'-bipyrrole
  参考文献：
  名称：

  Photodynamic Antitumor Agents: .beta.-Methoxyethyl Groups Give Access to Functionalized Porphycenes and Enhance Cellular Uptake and Activity

  摘要：

  Porphycene photosensitizers bearing two or four methoxyethyl side chains were synthesized in nine steps from commercially available starting materials. Ether cleavage led to (hydroxyethyl)- and (bromoethyl)porphycenes that were converted to vinyl and benzo derivatives. Five of the side chain-functionalized porphycenes were biologically studied in comparison with two tetra-n-propylporphycenes. Porphycenes were incorporated in small unilamellar liposomes and incubated with cultivated SSK2 murine fibrosarcoma cells. Cellular uptake and phototoxicity 24 h after 5 J/cm(2) laser light treatment were determined. The porphycenes tested were between 17 and 220 times more photodynamically active than the currently clinically used sensitizer Photofrin, although extinction coefficients of the porphycenes' irradiated bands are only approximately 10-fold higher. The LD(50) concentration for SSK2 cells in the incubation medium was as low as (8.5 +/- 2.8) x 10(-9) M for tetrakis(methoxyethyl)porphycene. Two methoxy or hydroxy groups enhanced cellular uptake, three or four methoxy groups both enhanced and accelerated cellular uptake of tetraalkylporphycenes. Half-life times of the uptake processes varied between (0.14 +/- 0.04) and (14 +/- 4) h and cellular saturation levels between (1.2 +/- 0.2) and (26 +/- 3) pmol/10(5) cells. When individual uptake rates were accounted for, all porphycenes had a similar ''cellular'' phototoxicity, pointing toward a common mechanism of action. Evidence is presented for the assumption that cell membranes are the primary targets of the tested porphycenes and that membrane solubility may play a critical role in their photodynamic efficiency. The results show that nonionic polar side chain functionalities can strongly enhance cellular uptake and antitumor activity of lipophilic porphyrinoids and thus that the known lipophilicity/activity relationship can be reversed for very hydrophobic sensitizers.

  DOI：

  10.1021/jm00043a019

文献信息

• Palladium(0) catalyzed 2,2′-bipyrrole syntheses
  作者：Lijuan Jiao、Erhong Hao、Frank R. Fronczek、M. Graça H. Vicente、Kevin M. Smith

  DOI：10.1142/s1088424611003355

  日期：2011.5

  Several 2-iodopyrroles are used in Pd (0) catalyzed homocoupling reactions at room temperature in the presence of water to efficiently synthesize 2,2′-bipyrroles. These 2,2′-bipyrroles are strongly luminous materials and have high fluorescence quantum yields.

  几种 2-碘吡咯用于 Pd (0) 催化的同源偶联反应，在室温和水的存在下有效合成 2,2'-联吡咯。这些2,2'-联吡咯是强发光材料，具有高荧光量子产率。
• Photodynamic Antitumor Agents: .beta.-Methoxyethyl Groups Give Access to Functionalized Porphycenes and Enhance Cellular Uptake and Activity
  作者：Clemens Richert、Jurina M. Wessels、Martin Mueller、Michael Kisters、Thomas Benninghaus、Alwin E. Goetz

  DOI：10.1021/jm00043a019

  日期：1994.8

  Porphycene photosensitizers bearing two or four methoxyethyl side chains were synthesized in nine steps from commercially available starting materials. Ether cleavage led to (hydroxyethyl)- and (bromoethyl)porphycenes that were converted to vinyl and benzo derivatives. Five of the side chain-functionalized porphycenes were biologically studied in comparison with two tetra-n-propylporphycenes. Porphycenes were incorporated in small unilamellar liposomes and incubated with cultivated SSK2 murine fibrosarcoma cells. Cellular uptake and phototoxicity 24 h after 5 J/cm(2) laser light treatment were determined. The porphycenes tested were between 17 and 220 times more photodynamically active than the currently clinically used sensitizer Photofrin, although extinction coefficients of the porphycenes' irradiated bands are only approximately 10-fold higher. The LD(50) concentration for SSK2 cells in the incubation medium was as low as (8.5 +/- 2.8) x 10(-9) M for tetrakis(methoxyethyl)porphycene. Two methoxy or hydroxy groups enhanced cellular uptake, three or four methoxy groups both enhanced and accelerated cellular uptake of tetraalkylporphycenes. Half-life times of the uptake processes varied between (0.14 +/- 0.04) and (14 +/- 4) h and cellular saturation levels between (1.2 +/- 0.2) and (26 +/- 3) pmol/10(5) cells. When individual uptake rates were accounted for, all porphycenes had a similar ''cellular'' phototoxicity, pointing toward a common mechanism of action. Evidence is presented for the assumption that cell membranes are the primary targets of the tested porphycenes and that membrane solubility may play a critical role in their photodynamic efficiency. The results show that nonionic polar side chain functionalities can strongly enhance cellular uptake and antitumor activity of lipophilic porphyrinoids and thus that the known lipophilicity/activity relationship can be reversed for very hydrophobic sensitizers.