7-hydroxymethyl-12H-5,11a-diaza-dibenzo[b,h]fluoren-11-one

• 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: 7-hydroxymethyl-12H-5,11a-diaza-dibenzo[b,h]fluoren-11-one
• 英文别名: 22-hydroxyacuminatine；19-(hydroxymethyl)-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15,17,19-nonaen-14-one
• 化学式: C₂₀H₁₄N₂O₂
• 分子量: 314.343
• InChiKey: FIAAPZRVXZOWNP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  53.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 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 115.0h， 生成 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

文献信息

• Total Synthesis of Camptothecin and Related Natural Products by a Flexible Strategy
  作者：Ke Li、Jinjie Ou、Shuanhu Gao

  DOI：10.1002/anie.201607832

  日期：2016.11.14

  strategy for constructing natural products containing indolizinone or quinolizinone scaffolds and their analogues was developed, which was based on a cascade exo hydroamination followed by spontaneous lactamization. This method was applied in the total synthesis of camptothecin in nine steps in a new ring‐forming approach. It was also used to efficiently prepare five biogenetically or structurally related

  开发了一种灵活的策略来构建包含吲哚嗪 酮或喹啉嗪酮支架及其类似物的天然产物，该策略基于级联外加氢胺化，然后进行自发内酰胺化。该方法以一种新的成环方法，通过九个步骤应用于喜树碱的全合成。它也可用于有效制备五种与生物遗传或结构相关的天然生物碱，包括22-羟基氨甲碱，羟巴马汀，去甲肾上腺素，naucleficine和nauclefine，以及35种类似天然产物的分子。我们认为，该方法及其制备的小分子文库可以为研究喜树碱和Nauclea天然产物的生物活性开辟新的途径。
• Total synthesis of the cytotoxic alkaloid 22-hydroxyacuminatine
  作者：Zhongze Ma、David Y.W. Lee

  DOI：10.1016/j.tetlet.2004.07.061

  日期：2004.8

  The total synthesis of the cytotoxic alkaloid 22-hydroxyacuminatine has been achieved in 14.9% overall yield starting from 2-methylcinnamic acid via the key intermediate 5-ethoxymethylisoquinolin-1-one.

  从2-甲基肉桂酸经关键中间体5-乙氧基甲基异喹啉-1-酮开始，已以14.9％的总收率实现了细胞毒性生物碱22-羟基氨基胍的总合成。
• Concise synthesis of 22-hydroxyacuminatine, cytotoxic camptothecinoid from Camptotheca acuminata, by pyridone benzannulation
  作者：Matej Babjak、Alice Kanazawa、Regan J. Anderson、Andrew E. Greene

  DOI：10.1039/b516154a

  日期：——

  A short, efficient synthesis of 22-hydroxyacuminatine, starting from a readily accessible hydroxy pyridone, is presented; key steps include a Heck coupling with methyl pentadienoate, a flash vacuum pyrolytic cyclization, and a Friedlander condensation.

  从容易获得的羟基吡啶酮开始，提出了一种短而有效的22-羟基氨基丁酸合成方法。关键步骤包括与戊二烯酸甲酯的Heck偶联，快速真空热解环化和Friedlander缩合。
• 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.