Methyl 1,2-bis(4-hydroxy-3-methoxyphenyl)-9-methoxy-8-propan-2-yloxy-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carboxylate | 897017-95-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: Methyl 1,2-bis(4-hydroxy-3-methoxyphenyl)-9-methoxy-8-propan-2-yloxy-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carboxylate
• CAS: 897017-95-7
• 化学式: C₃₂H₃₃NO₈
• 分子量: 559.616
• InChiKey: GDZLUWDPUMMVKI-UHFFFAOYSA-N

物化性质

• 熔点：
  244-246 °C(Solvent: Acetonitrile)
• 沸点：
  720.3±60.0 °C(predicted)
• 密度：
  1.28±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  41
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Methyl 1,2-bis(4-hydroxy-3-methoxyphenyl)-9-methoxy-8-propan-2-yloxy-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carboxylate 在 三氯化铝 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 生成 8-Hydroxy-1,2-bis-(4-hydroxy-3-methoxy-phenyl)-9-methoxy-5,6-dihydro-pyrrolo[2,1-a]isoquinoline-3-carboxylic acid methyl ester
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship Study of Potent Cytotoxic Analogues of the Marine Alkaloid Lamellarin D

  摘要：

  The marine alkaloid, Lamellarin D (Lam-D), has shown potent cytotoxicity in numerous cancer cell lines and was recently identified as a potent topoisomerase I inhibitor. A library of open lactone analogues of Lam-D was prepared from a methyl 5,6-dihydropyrrolo[2,1-a] isoquinoline-3- carboxylate scaffold (1) by introducing various aryl groups through sequential and regioselective bromination, followed by Pd(0)-catalyzed Suzuki cross-coupling chemistry. The compounds were obtained in a 24-44% overall yield, and tested in a panel of three human tumor cell lines, MDA-MB-231 (breast), A-549 (lung), and HT-29 (colon), to evaluate their cytotoxic potential. From these data, the SAR study concluded that more than 75% of the open-chain Lam-D analogues tested showed cytotoxicity in a low micromolar GI(50) range.

  DOI：

  10.1021/jm0602458
• 作为产物：
  描述：

  2-吡咯甲酸甲酯 在 bis-triphenylphosphine-palladium(II) chloride 、 四(三苯基膦)钯 N-溴代丁二酰亚胺(NBS) 、 sodium hydride 、 sodium carbonate 、 potassium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 Methyl 1,2-bis(4-hydroxy-3-methoxyphenyl)-9-methoxy-8-propan-2-yloxy-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carboxylate
  参考文献：
  名称：

  5,6-Dihydropyrrolo[2,1-b]isoquinolines as scaffolds for synthesis of lamellarin analogues

  摘要：

  Efficient modular synthetic routes to open chain marine alkaloids such as lamellarins have been developed. 5,6-Dihydropyrrolo[2, 1-b]isoquinoline scaffolds were prepared, and protocols enabling regioselective bromination followed by Suzuki cross-coupling were established for the introduction of aryl groups onto the 2- and 3-positions. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2005.01.145

文献信息

• Synthesis and Structure−Activity Relationship Study of Potent Cytotoxic Analogues of the Marine Alkaloid Lamellarin D
  作者：Daniel Pla、Antonio Marchal、Christian A. Olsen、Andrés Francesch、Carmen Cuevas、Fernando Albericio、Mercedes Álvarez

  DOI：10.1021/jm0602458

  日期：2006.6.1

  The marine alkaloid, Lamellarin D (Lam-D), has shown potent cytotoxicity in numerous cancer cell lines and was recently identified as a potent topoisomerase I inhibitor. A library of open lactone analogues of Lam-D was prepared from a methyl 5,6-dihydropyrrolo[2,1-a] isoquinoline-3- carboxylate scaffold (1) by introducing various aryl groups through sequential and regioselective bromination, followed by Pd(0)-catalyzed Suzuki cross-coupling chemistry. The compounds were obtained in a 24-44% overall yield, and tested in a panel of three human tumor cell lines, MDA-MB-231 (breast), A-549 (lung), and HT-29 (colon), to evaluate their cytotoxic potential. From these data, the SAR study concluded that more than 75% of the open-chain Lam-D analogues tested showed cytotoxicity in a low micromolar GI(50) range.
• 5,6-Dihydropyrrolo[2,1-b]isoquinolines as scaffolds for synthesis of lamellarin analogues
  作者：Christian A. Olsen、Núria Parera、Fernando Albericio、Mercedes Álvarez

  DOI：10.1016/j.tetlet.2005.01.145

  日期：2005.3

  Efficient modular synthetic routes to open chain marine alkaloids such as lamellarins have been developed. 5,6-Dihydropyrrolo[2, 1-b]isoquinoline scaffolds were prepared, and protocols enabling regioselective bromination followed by Suzuki cross-coupling were established for the introduction of aryl groups onto the 2- and 3-positions. (C) 2005 Elsevier Ltd. All rights reserved.