4'-demethyl-4β-(4"-chloroanilino)-4-desoxypodophyllotoxin | 125830-40-2

• 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: 4'-demethyl-4β-(4"-chloroanilino)-4-desoxypodophyllotoxin
• 英文别名: (5S,5aS,8aR,9R)-5-(4-chloroanilino)-9-(4-hydroxy-3,5-dimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one
• CAS: 125830-40-2
• 化学式: C₂₇H₂₄ClNO₇
• 分子量: 509.943
• InChiKey: IFZQZYOZNMLRTG-LVEBQJTPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  95.5
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  鬼臼毒素 在 氢溴酸 、 四丁基碘化铵 、 三乙胺 、 barium carbonate 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 56.25h， 生成 4'-demethyl-4β-(4"-chloroanilino)-4-desoxypodophyllotoxin
  参考文献：
  名称：

  4β-苯胺基-4'-去甲基表鬼臼毒素的有效方法：NPF和W-68的合成

  摘要：

  通过在4-溴表鬼臼毒素的置换反应中使用Bu 4 N + T，获得了具有明显立体选择性和提高产量的4β取代鬼臼毒素同类物。通过这种方法可以高收率制备DNA拓扑异构酶II抑制剂NPF和W-68。

  DOI：

  10.1016/0040-4039(96)00546-1

文献信息

• Antitumor agents. 111. New 4-hydroxylated and 4-halogenated anilino derivatives of 4'-demethylepipodophyllotoxin as potent inhibitors of human DNA topoisomerase II
  作者：Kuo Hsiung Lee、Scott A. Beers、Masami Mori、Zhe Qing Wang、Yao Haur Kuo、Li Li、Su Ying Liu、Jang Yang Chang、Fu Sheng Han、Yung Chi Cheng

  DOI：10.1021/jm00167a013

  日期：1990.5

  A series of C-4 hydroxylated and halogenated anilino derivatives of epipodophyllotoxin or 4'-demethylepipodophyllotoxin 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. Compounds 11-17 and 22 are more potent than etoposide in causing DNA breakage, while compounds 11-13, 15, 16, and 20 are as active or more active than etoposide in their inhibition of the human DNA topoisomerase II. The cytotoxicity in KB cells appears to have no direct correlation with their ability to inhibit DNA topoisomerase II and to cause protein-linked DNA breaks in cells.
• A one-pot, efficient and facile synthesis of 4β-arylaminopodophyllotoxins: synthesis of NPF and GL-331 as DNA topoisomerase II inhibitors
  作者：Ahmed Kamal、B.Ashwini Kumar、M. Arifuddin

  DOI：10.1016/j.tetlet.2003.09.110

  日期：2003.11

  A series of 4beta-arylamino-4'-O-demethylepipodophyllotoxins and 4beta-arylaminopodophyllotoxins have been synthesized with significant stereoselectivity and improved yields by employing the BF3 . OEt2/Nal reagent system. Compounds NPF, GL-331 and other DNA topoisomerase 11 inhibitors have been prepared in good to excellent yields by employing this methodology. (C) 2003 Elsevier Ltd. All rights reserved.
• Facile and efficient one-pot synthesis of 4β-arylaminopodophyllotoxins: synthesis of DNA topoisomerase II inhibitors (NPF and W-68)
  作者：Ahmed Kamal、N. Laxman、G. Ramesh

  DOI：10.1016/s0960-894x(00)00407-8

  日期：2000.9

  A series of 4 beta-arylamino-4'-O-demethylepipodophyllotoxins and 4 beta-arylaminoepipodophyllotoxins have been synthesized with significant stereoselectivity and improved yields by employing the methanesulphonic acid/sodium iodide reagent system. Compounds NPF, W-68 and other DNA topoisomerase II inhibitors are prepared in good to excellent yields by this method and these are active or more active than etoposide in their inhibition of the human DNA topoisomerase II. (C) 2000 Elsevier Science Ltd. All rights reserved.
• LEE, KUO-HSIUNG;BEERS, SCOTT A.;MORI, MASAMI;WANG, ZHE-QING;KUO, YAO-HAUR+, J. MED. CHEM., 33,(1990) N, C. 1364-1368
  作者：LEE, KUO-HSIUNG、BEERS, SCOTT A.、MORI, MASAMI、WANG, ZHE-QING、KUO, YAO-HAUR+

  DOI：——

  日期：——
• An efficient method for 4β-anilino-4′-demethylepipodophyllotoxins: Synthesis of NPF and W-68
  作者：Ahmed Kamal、N.Lakshmi Gayatri

  DOI：10.1016/0040-4039(96)00546-1

  日期：1996.5

  4β-Substituted podophyllotoxin congeners have been obtained with significant stereoselectivity and improved yields by employing Bu4N+T in the displacement reaction of the 4-bromoepipodophyllotoxin. The DNA topoisomerase II inhibitors, NPF and W-68 have been prepared in good yields by this method.

  通过在4-溴表鬼臼毒素的置换反应中使用Bu 4 N + T，获得了具有明显立体选择性和提高产量的4β取代鬼臼毒素同类物。通过这种方法可以高收率制备DNA拓扑异构酶II抑制剂NPF和W-68。