2'-chloro-4'-demethylpodophyllotoxin | 138261-31-1

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 木脂素内酯
• 英文名称: 2'-chloro-4'-demethylpodophyllotoxin
• 英文别名: 2'-chloro-4'-demethylepipodophyllotoxin；2'-chloro-4'-demethoxyepipodophyllotoxin；2'-chloro-4′-demethylepipodophyllotoxin；(5S,5aR,8aR,9S)-9-(2-chloro-4-hydroxy-3,5-dimethoxyphenyl)-5-hydroxy-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one
• CAS: 138261-31-1
• 化学式: C₂₁H₁₉ClO₈
• 分子量: 434.83
• InChiKey: BZJLGKCNUIRGRX-TWUUUVDRSA-N

物化性质

• 沸点：
  626.6±55.0 °C(Predicted)
• 密度：
  1.505±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2'-chloro-4'-demethylpodophyllotoxin 在 氢溴酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 4β-bromo-2'-chloro-4'-O-demethyl-4-desoxypodophyllotoxin
  参考文献：
  名称：

  Antitumor agents. 123. Synthesis and human DNA topoisomerase II inhibitory activity of 2'-chloro derivatives of etoposide and 4.beta.-(arylamino)-4'-O-demethylpodophyllotoxins

  摘要：

  The 2'-chloro derivatives of etoposide and 4-beta-(arylamino)-4'-O-demethylpodophyllotoxins have been synthesized and evaluated for their inhibitory activity against the human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. The results showed that none of the compounds are active as a result of the C-2' chloro substitution on ring E. This would suggest that the free rotation of ring E is essential for the aforementioned enzyme inhibitory activity. In addition, these 2'-chloro derivatives showed no significant cytotoxicity (KB).

  DOI：

  10.1021/jm00083a009
• 作为产物：
  描述：

  苦鬼臼毒素 在 N-氯代丁二酰亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以85%的产率得到2'-chloro-4'-demethylpodophyllotoxin
  参考文献：
  名称：

  Insight into dihalogenation of E-ring of podophyllotoxins, and their acyloxyation derivatives at the C4 position as insecticidal agents

  摘要：

  Unexpected sequential E-ring dihalogenation of podophyllotoxin analogues is reported. It demonstrated that a chlorine/bromine atom was prior introduced at the C2' position of podophyllotoxin, and the corresponding free rotation of E-ring around the C1-C1' bond of 2'-chloro or 2'-bromopodophyllotoxin was restricted. When 2'-chloro or 2'-bromopodophyllotoxin reacted with N-chlorosuccinimide (NCS), the chlorine atom was regioselectively introduced at their C6' position on the E-ring. Whereas 2'-chloro or 2'-bromopodophyllotoxin reacted with NBS, the bromine atom was regioselectively introduced at their C5 position on the B-ring. When 2'-chloropodophyllotoxin reacted with different carboxylic acids in the presence of BF3 center dot Et2O, the steric effect of its E-ring for stereoselective synthesis of 4 beta-acyloxy-2'-chloropodophyllotoxin derivatives was observed. The insecticidal activity of 2'(2',6')-(di)halogen-substituted podophyllotoxin derivatives were evaluated with Mythimna separata Walker. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.044

文献信息

• Synthesis of some ester derivatives of 4′-demethoxyepipodophyllotoxin/2′-chloro-4′-demethoxyepipodophyllotoxin as insecticidal agents against oriental armyworm, Mythimna separata Walker
  作者：Jiulin Huang、Ming Xu、Shaochen Li、Jiani He、Hui Xu

  DOI：10.1016/j.bmcl.2016.12.026

  日期：2017.2

  Podophyllotoxin is a naturally occurring non-alkaloid toxin isolated from the roots and rhizomes of Podophyllum peltatum and P. hexandrum. In continuation of our program aimed at the discovery and development of natural product-based insecticides, two series of ester derivatives of 4′-demethoxyepipodophyllotoxin/2′-chloro-4′-demethoxyepipodophyllotoxin were prepared. The structures of the target compounds

  鬼臼毒素是一种天然存在的非生物碱毒素，是从鬼臼和六角茴香的根和根茎中分离出来的。在我们旨在发现和开发基于天然产物的杀虫剂的程序的继续中，制备了两个系列的4'-脱甲氧基表鬼臼毒素/ 2'-氯-4'-脱甲氧基表鬼臼毒素酯衍生物。目标化合物的结构通过1 H NMR，IR，旋光度和mp很好地表征。通过单晶X射线衍射进一步确定了8j的精确三维结构信息。对它们的杀虫活性进行了抗Mythimna separata的测试。沃克。这些化合物显示出延迟的杀虫活性。在所有衍生物中，某些化合物比过千金丹对分离的分枝杆菌表现出更强的杀虫活性。特别是化合物8k和9k表现出最强的活性，最终死亡率为71.4％。他们的结构-活动关系进行了讨论。
• Synthesis and evaluation of etoposide and podophyllotoxin analogs against topoisomerase IIα and HCT-116 cells
  作者：Matthew B. Murphy、Priyanka Kumar、Amber M. Bradley、Christopher E. Barton、Joseph E. Deweese、Susan L. Mercer

  DOI：10.1016/j.bmc.2020.115773

  日期：2020.11

  studies suggest halogenation at the C-2’ position of etoposide reduces metabolism. Halogens were introduced into the C-2’ position by electrophilic aromatic halogenation onto etoposide (ETOP, 1), podophyllotoxin (PPT, 2), and 4-dimethylepipodophyllotoxin (DMEP, 3), and to bridge the gap of knowledge regarding the activity of these metabolically stable analogs. Five halogenated analogs (6-10) were synthesized

  依托泊苷是针对人类II型拓扑异构酶的广泛使用的抗癌药。有证据表明，髓样祖细胞中依托泊苷的代谢与白血病发展有关的易位有关。先前的研究表明，依托泊苷C-2'位置的卤化作用会降低新陈代谢。卤素通过亲核性依托泊苷（ETOP，1），鬼臼毒素（PPT，2）和4-二甲基表鬼臼毒素（DMEP，3）的亲电子卤化作用引入C-2'位置，并弥合了有关这些代谢稳定的类似物。合成了五个卤代类似物（6-10）。类似物8-10显示出抑制DNA松弛的可变能力。类似物9是唯一显示Top2介导的DNA切割的浓度依赖性增强的类似物。剂量反应分析结果表明，8和10在降低培养物中HCT-116和A549癌细胞系的生存力方面最有效。HCT-116细胞中8和10的流式细胞术提供了指示凋亡的亚G1细胞群体的证据。两者合计，这些结果表明依托泊苷及其前体的C-2'卤化尽管在代谢上稳定，但相对于依托泊苷而言降低了总体活性。
• Synthesis of 4β-acyloxypodophyllotoxin analogs modified in the C and E rings as insecticidal agents against Mythimna separata Walker
  作者：Xiaoyan Zhi、Xiang Yu、Chun Yang、Guodong Ding、Hui Chen、Hui Xu

  DOI：10.1016/j.bmcl.2013.12.105

  日期：2014.2

  To discover the new natural-product-based insecticidal agents, four series of sixty novel 4 beta-acyloxypodophyllotoxin analogs modified in the C and E rings were prepared, and their insecticidal activity was tested against the pre-third-instar larvae of oriental armyworm, Mythimna separata (Walker) in vivo at the concentration of 1 mg/mL. It demonstrated that the position of the dioxo group on the E-ring of 4'-demethylepipodophyllotoxin was regioselectively controlled by the chlorine atom at its C-2' position when 2'-chloro-4'-demethylepipodophyllotoxin was oxidized by sodium periodate. Among all the derivatives, IIIi exhibited the best potent insecticidal activity with the final mortality rate of 63.3%. To alkylacyloxy series, the proper length of the side chain at the C-4 position of Ia-g, IIa-g and IIIa-g was important for their insecticidal activity. (C) 2013 Elsevier Ltd. All rights reserved.
• Antitumor agents. 123. Synthesis and human DNA topoisomerase II inhibitory activity of 2'-chloro derivatives of etoposide and 4.beta.-(arylamino)-4'-O-demethylpodophyllotoxins
  作者：Hong Hu、Su Ying Liu、Yung Chi Cheng、Kuo Hsiung Lee、Zhe Qing Wang

  DOI：10.1021/jm00083a009

  日期：1992.3

  The 2'-chloro derivatives of etoposide and 4-beta-(arylamino)-4'-O-demethylpodophyllotoxins have been synthesized and evaluated for their inhibitory activity against the human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. The results showed that none of the compounds are active as a result of the C-2' chloro substitution on ring E. This would suggest that the free rotation of ring E is essential for the aforementioned enzyme inhibitory activity. In addition, these 2'-chloro derivatives showed no significant cytotoxicity (KB).
• Insight into dihalogenation of E-ring of podophyllotoxins, and their acyloxyation derivatives at the C4 position as insecticidal agents
  作者：Zhiping Che、Xiang Yu、Lingling Fan、Hui Xu

  DOI：10.1016/j.bmcl.2013.08.044

  日期：2013.10

  Unexpected sequential E-ring dihalogenation of podophyllotoxin analogues is reported. It demonstrated that a chlorine/bromine atom was prior introduced at the C2' position of podophyllotoxin, and the corresponding free rotation of E-ring around the C1-C1' bond of 2'-chloro or 2'-bromopodophyllotoxin was restricted. When 2'-chloro or 2'-bromopodophyllotoxin reacted with N-chlorosuccinimide (NCS), the chlorine atom was regioselectively introduced at their C6' position on the E-ring. Whereas 2'-chloro or 2'-bromopodophyllotoxin reacted with NBS, the bromine atom was regioselectively introduced at their C5 position on the B-ring. When 2'-chloropodophyllotoxin reacted with different carboxylic acids in the presence of BF3 center dot Et2O, the steric effect of its E-ring for stereoselective synthesis of 4 beta-acyloxy-2'-chloropodophyllotoxin derivatives was observed. The insecticidal activity of 2'(2',6')-(di)halogen-substituted podophyllotoxin derivatives were evaluated with Mythimna separata Walker. (C) 2013 Elsevier Ltd. All rights reserved.