14-Oxo-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15,17,19-nonaene-19-carbaldehyde | 850415-08-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 14-Oxo-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15,17,19-nonaene-19-carbaldehyde
• 英文别名: 14-oxo-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15,17,19-nonaene-19-carbaldehyde
• CAS: 850415-08-6
• 化学式: C₂₀H₁₂N₂O₂
• 分子量: 312.327
• InChiKey: QPSJLGLIEYKXFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  50.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  14-Oxo-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15,17,19-nonaene-19-carbaldehyde 在 二异丁基氢化铝 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以67%的产率得到7-hydroxymethyl-12H-5,11a-diaza-dibenzo[b,h]fluoren-11-one
  参考文献：
  名称：

  Total Synthesis and Biological Evaluation of 22-Hydroxyacuminatine

  摘要：

  A total synthesis of 22-hydroxyacuminatine, a cytotoxic alkaloid isolated from Camptotheca acuminata, is reported. The key step in the synthesis involves the reaction of 2,3-dihydro-1H-pyrrolo[3,4-b]quinoline with a brominated phthalide to generate a substituted pentacyclic 12H-5,11a-diazadibenzo[b,h]fluoren-11-one intermediate. Despite its structural resemblance to camptothecin and luotonin A, a biological evaluation of 22-hydroxyacuminatine in a topoisomerase I-deficient cell line P388/CPT45 has confirmed that the observed cytotoxicity is not due to topoisomerase I inhibition, even though 22-hydroxyacuminatine has a hydroxyl group that can theoretically hydrogen bond to Asp533. This result is consistent with the hypothesis that pi-pi stacking is more important than hydrogen-bonding interactions in determining topoisomerase I inhibitor binding in the ternary cleavage complex.

  DOI：

  10.1021/jm051116e
• 作为产物：
  描述：

  1-氧代-1,3-二氢异苯并呋喃-4-甲腈 在 吡啶 、 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 二异丁基氢化铝 作用下， 以 四氯化碳 、 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 113.0h， 生成 14-Oxo-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15,17,19-nonaene-19-carbaldehyde
  参考文献：
  名称：

  Total Synthesis and Biological Evaluation of 22-Hydroxyacuminatine

  摘要：

  A total synthesis of 22-hydroxyacuminatine, a cytotoxic alkaloid isolated from Camptotheca acuminata, is reported. The key step in the synthesis involves the reaction of 2,3-dihydro-1H-pyrrolo[3,4-b]quinoline with a brominated phthalide to generate a substituted pentacyclic 12H-5,11a-diazadibenzo[b,h]fluoren-11-one intermediate. Despite its structural resemblance to camptothecin and luotonin A, a biological evaluation of 22-hydroxyacuminatine in a topoisomerase I-deficient cell line P388/CPT45 has confirmed that the observed cytotoxicity is not due to topoisomerase I inhibition, even though 22-hydroxyacuminatine has a hydroxyl group that can theoretically hydrogen bond to Asp533. This result is consistent with the hypothesis that pi-pi stacking is more important than hydrogen-bonding interactions in determining topoisomerase I inhibitor binding in the ternary cleavage complex.

  DOI：

  10.1021/jm051116e

文献信息

• Total Synthesis and Biological Evaluation of 22-Hydroxyacuminatine
  作者：Xiangshu Xiao、Smitha Antony、Yves Pommier、Mark Cushman

  DOI：10.1021/jm051116e

  日期：2006.2.1

  A total synthesis of 22-hydroxyacuminatine, a cytotoxic alkaloid isolated from Camptotheca acuminata, is reported. The key step in the synthesis involves the reaction of 2,3-dihydro-1H-pyrrolo[3,4-b]quinoline with a brominated phthalide to generate a substituted pentacyclic 12H-5,11a-diazadibenzo[b,h]fluoren-11-one intermediate. Despite its structural resemblance to camptothecin and luotonin A, a biological evaluation of 22-hydroxyacuminatine in a topoisomerase I-deficient cell line P388/CPT45 has confirmed that the observed cytotoxicity is not due to topoisomerase I inhibition, even though 22-hydroxyacuminatine has a hydroxyl group that can theoretically hydrogen bond to Asp533. This result is consistent with the hypothesis that pi-pi stacking is more important than hydrogen-bonding interactions in determining topoisomerase I inhibitor binding in the ternary cleavage complex.