(1R,2R,13S)-18,19-dimethoxy-21-methyl-11,21-diazapentacyclo[11.7.1.02,11.04,9.015,20]henicosa-4,6,8,15(20),16,18-hexaen-12-one | 879288-07-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (1R,2R,13S)-18,19-dimethoxy-21-methyl-11,21-diazapentacyclo[11.7.1.02,11.04,9.015,20]henicosa-4,6,8,15(20),16,18-hexaen-12-one
• CAS: 879288-07-0
• 化学式: C₂₂H₂₄N₂O₃
• 分子量: 364.444
• InChiKey: YQPOWFLYZSZMTE-UWVAXJGDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  42
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1R,2R,13S)-18,19-dimethoxy-21-methyl-11,21-diazapentacyclo[11.7.1.02,11.04,9.015,20]henicosa-4,6,8,15(20),16,18-hexaen-12-one 在 二异丁基氢化铝 、 溶剂黄146 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 3.0h， 生成 (1R,2R,12R,13S)-18,19-dimethoxy-21-methyl-11,21-diazapentacyclo[11.7.1.02,11.04,9.015,20]henicosa-4,6,8,15(20),16,18-hexaene-12-carbonitrile
  参考文献：
  名称：

  Synthesis and inhibition of cancer cell proliferation of (1,3′)-bis-tetrahydroisoquinolines and piperazine systems

  摘要：

  Some (1,3')-bis-tetrahydroisoquinolines were reported as scaffold intermediates for the synthesis of pentacyclic piperazine core alkaloids and their cytotoxicity against cancerous cell lines was evaluated. The NMR and X-ray structural assignments revealed an anti C3-C11 backbone stereochemistry of piperazine structures. Inhibition of cancer cell proliferation of (1,3')-bis-tetrahydroisoquinoline scaffolds and pentacyclic piperazine systems was assessed against three human cancer cell lines (K562 myelogenous leukemia, A549 lung carcinoma, MCF-7 breast adenocarcinoma) and both mouse tumor cell lines of blood (P388) and lymphocytic (L1210) leukemia with considerable activity against the latter. The cell cycle analysis was also studied by flow cytometry measurement on K562 cell line. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.01.108
• 作为产物：
  描述：

  methyl (1R,3S)-7,8-dimethoxy-2-methyl-1-[(3R)-2-[(2-methylpropan-2-yl)oxycarbonyl]-3,4-dihydro-1H-isoquinolin-3-yl]-3,4-dihydro-1H-isoquinoline-3-carboxylate 在 lithium hydroxide 、 五氟苯基二苯基磷酸酯 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.5h， 生成 (1R,2R,13S)-18,19-dimethoxy-21-methyl-11,21-diazapentacyclo[11.7.1.02,11.04,9.015,20]henicosa-4,6,8,15(20),16,18-hexaen-12-one
  参考文献：
  名称：

  （1,3'）-双四氢异喹啉的合成研究：哌嗪核心生物碱的五环类似物

  摘要：

  （1,3'）-双四氢异喹啉的合成研究据报道是通过连续的Pictet-Spengler环化作用和分子内肽偶联合成邻苯二酚和邻苯二酚五环结构类似物的关键中间体。l-DOPA衍生物与N-保护的α-氨基醛之间的直接Pictet-Spengler反应首先扩展到顺式的合成-（1,3'）-双四氢异喹啉。引入所需的氨基酸部分后，有效的六元环分子内肽偶联产生了哌嗪衍生物结构。通过NMR和X射线光谱法证实了完整的结构归属。然而，N-保护的α-氨基醛的光学完整性似乎对反应条件敏感。Pentacylic结构，具有抗C3-C11骨干立体化学，从环合制得的对-和邻位-与3-OH基团的L-DOPA衍生物。

  DOI：

  10.1016/j.tetlet.2005.12.056

文献信息

• Synthetic investigations of (1,3′)-bistetrahydroisoquinolines: towards pentacyclic analogues of piperazine core alkaloids
  作者：Sylvain Aubry、Stéphane Pellet-Rostaing、Bernard Fenet、Marc Lemaire

  DOI：10.1016/j.tetlet.2005.12.056

  日期：2006.2

  lines are reported as the key intermediates for the synthesis of ecteinascidin and phthalascidin pentacyclic structure analogues through successive Pictet–Spengler cyclization and intramolecular peptide coupling. The direct Pictet–Spengler reaction between a derivative of l-DOPA and N-protected-α-aminoaldehyde was first extended to the synthesis of cis-(1,3′)-bistetrahydroisoquinoline. After introduction

  （1,3'）-双四氢异喹啉的合成研究据报道是通过连续的Pictet-Spengler环化作用和分子内肽偶联合成邻苯二酚和邻苯二酚五环结构类似物的关键中间体。l-DOPA衍生物与N-保护的α-氨基醛之间的直接Pictet-Spengler反应首先扩展到顺式的合成-（1,3'）-双四氢异喹啉。引入所需的氨基酸部分后，有效的六元环分子内肽偶联产生了哌嗪衍生物结构。通过NMR和X射线光谱法证实了完整的结构归属。然而，N-保护的α-氨基醛的光学完整性似乎对反应条件敏感。Pentacylic结构，具有抗C3-C11骨干立体化学，从环合制得的对-和邻位-与3-OH基团的L-DOPA衍生物。
• Synthesis and inhibition of cancer cell proliferation of (1,3′)-bis-tetrahydroisoquinolines and piperazine systems
  作者：Sylvain Aubry、Stéphane Pellet-Rostaing、Jérémie Fournier dit Chabert、Sylvie Ducki、Marc Lemaire

  DOI：10.1016/j.bmcl.2007.01.108

  日期：2007.5

  Some (1,3')-bis-tetrahydroisoquinolines were reported as scaffold intermediates for the synthesis of pentacyclic piperazine core alkaloids and their cytotoxicity against cancerous cell lines was evaluated. The NMR and X-ray structural assignments revealed an anti C3-C11 backbone stereochemistry of piperazine structures. Inhibition of cancer cell proliferation of (1,3')-bis-tetrahydroisoquinoline scaffolds and pentacyclic piperazine systems was assessed against three human cancer cell lines (K562 myelogenous leukemia, A549 lung carcinoma, MCF-7 breast adenocarcinoma) and both mouse tumor cell lines of blood (P388) and lymphocytic (L1210) leukemia with considerable activity against the latter. The cell cycle analysis was also studied by flow cytometry measurement on K562 cell line. (c) 2007 Elsevier Ltd. All rights reserved.