methyl 2-(2,4-dihydroxy-5-methoxyphenyl)-8-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-9-methoxypyrrolo[2,1-a]isoquinoline-3-carboxylate | 867313-44-8

• 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 2-(2,4-dihydroxy-5-methoxyphenyl)-8-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-9-methoxypyrrolo[2,1-a]isoquinoline-3-carboxylate
• CAS: 867313-44-8
• 化学式: C₂₉H₂₅NO₉
• 分子量: 531.519
• InChiKey: QQCHDXYOYDDRFY-UHFFFAOYSA-N

物化性质

• 熔点：
  163-166 °C(Solvent: Acetonitrile)
• 密度：
  1.41±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：
  39
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  139
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl 2-(2,4-dihydroxy-5-methoxyphenyl)-8-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-9-methoxypyrrolo[2,1-a]isoquinoline-3-carboxylate 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以75%的产率得到lamellarin D
  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 、 四(三苯基膦)钯 potassium phosphate 、 N-溴代丁二酰亚胺(NBS) 、 三氯化铝 、 sodium hydride 、 sodium carbonate 、 potassium carbonate 、 三苯基膦 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 70.58h， 生成 methyl 2-(2,4-dihydroxy-5-methoxyphenyl)-8-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-9-methoxypyrrolo[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

• 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).