methyl 8-isopropoxy-9-methoxy-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carboxylate | 850346-72-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: methyl 8-isopropoxy-9-methoxy-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carboxylate
• 英文别名: methyl 9-methoxy-8-propan-2-yloxy-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carboxylate
• CAS: 850346-72-4
• 化学式: C₁₈H₂₁NO₄
• 分子量: 315.369
• InChiKey: KFINPNZBYVFYLR-UHFFFAOYSA-N

物化性质

• 熔点：
  109 °C
• 沸点：
  473.7±45.0 °C(predicted)
• 密度：
  1.20±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  49.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 8-isopropoxy-9-methoxy-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carboxylate 在 四(三苯基膦)钯 N-溴代丁二酰亚胺(NBS) 、 sodium carbonate 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.5h， 生成 methyl 2-bromo-8-isopropoxy-1-(4-isopropoxy-3-methoxyphenyl)-9-methoxy-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carboxylate
  参考文献：
  名称：

  Modular Total Synthesis of Lamellarin D

  摘要：

  A modular total synthesis of lamellarin D, a marine alkaloid with potent cytotoxic as well as topoisomerase I inhibition properties, has been accomplished. A sequential and regioselective bromination/Suzuki cross-coupling procedure was applied for the introduction of aryl groups at positions 1 and 2 of scaffold 1. Microwave-assisted 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) oxidation to yield pyrroloisoquinoline 15, followed by phenol group deprotection and subsequent lactonization, gave lamellarin D (18% in eight steps from 1).

  DOI：

  10.1021/jo051083a
• 作为产物：
  描述：

  2-吡咯甲酸甲酯 在 bis-triphenylphosphine-palladium(II) chloride sodium hydride 、 potassium carbonate 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 methyl 8-isopropoxy-9-methoxy-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carboxylate
  参考文献：
  名称：

  Modular Total Synthesis of Lamellarin D

  摘要：

  A modular total synthesis of lamellarin D, a marine alkaloid with potent cytotoxic as well as topoisomerase I inhibition properties, has been accomplished. A sequential and regioselective bromination/Suzuki cross-coupling procedure was applied for the introduction of aryl groups at positions 1 and 2 of scaffold 1. Microwave-assisted 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) oxidation to yield pyrroloisoquinoline 15, followed by phenol group deprotection and subsequent lactonization, gave lamellarin D (18% in eight steps from 1).

  DOI：

  10.1021/jo051083a

文献信息

• 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.
• 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.
• Modular Total Synthesis of Lamellarin D
  作者：Daniel Pla、Antonio Marchal、Christian A. Olsen、Fernando Albericio、Mercedes Álvarez

  DOI：10.1021/jo051083a

  日期：2005.9.1

  A modular total synthesis of lamellarin D, a marine alkaloid with potent cytotoxic as well as topoisomerase I inhibition properties, has been accomplished. A sequential and regioselective bromination/Suzuki cross-coupling procedure was applied for the introduction of aryl groups at positions 1 and 2 of scaffold 1. Microwave-assisted 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) oxidation to yield pyrroloisoquinoline 15, followed by phenol group deprotection and subsequent lactonization, gave lamellarin D (18% in eight steps from 1).