3-bromopropyl (4aR,5S,6R,11bR)-2,2-dimethyl-6-(3,4,5-trimethoxyphenyl)-4a,5,6,11b-tetrahydro-4H-[1,3]benzodioxolo[5,6-h][1,3]benzodioxine-5-carboxylate | 1416574-55-4

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 芳基四氢萘木脂素
• 英文名称: 3-bromopropyl (4aR,5S,6R,11bR)-2,2-dimethyl-6-(3,4,5-trimethoxyphenyl)-4a,5,6,11b-tetrahydro-4H-[1,3]benzodioxolo[5,6-h][1,3]benzodioxine-5-carboxylate
• CAS: 1416574-55-4
• 化学式: C₂₈H₃₃BrO₉
• 分子量: 593.469
• InChiKey: UIUKOGLAXMPTNQ-YCXHYSRHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  90.9
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3-bromopropyl (4aR,5S,6R,11bR)-2,2-dimethyl-6-(3,4,5-trimethoxyphenyl)-4a,5,6,11b-tetrahydro-4H-[1,3]benzodioxolo[5,6-h][1,3]benzodioxine-5-carboxylate 在 草酰氯 、 potassium carbonate 、 对甲苯磺酸 、 二甲基亚砜 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 72.5h， 生成 3-(6-chloropurin-9-yl)propyl (7S,8R)-6-formyl-8-(3,4,5-trimethoxyphenyl)-7,8-dihydrobenzo[f][1,3]benzodioxole-7-carboxylate
  参考文献：
  名称：

  Lignopurines: A new family of hybrids between cyclolignans and purines. Synthesis and biological evaluation

  摘要：

  A new family of hybrids between cyclolignans related to podophyllic aldehyde, a non-lactonic cyclolignan, and purines were prepared and evaluated against several human tumour cell lines. Both fragments, cyclolignan and purine, were linked through aliphatic and aromatic chains. The influence on the cytotoxicity of the purine substitution and the nature of the linker is analyzed. The new family was slightly less cytotoxic than the parent podophyllic aldehyde, although the selectivity is maintained or even improved and among the linkers used, the presence of an aromatic ring gave the most potent and selective derivatives within the new series tested. Cell cycle and confocal studies demonstrate that these derivatives interfere with the tubulin polymerization and arrest cells at the G(2)/M phase, in the same way than the parent compounds podophyllotoxin and podophyllic aldehyde do. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.10.026
• 作为产物：
  描述：

  picropodophyllic acid 在 potassium carbonate 、 对甲苯磺酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 3-bromopropyl (4aR,5S,6R,11bR)-2,2-dimethyl-6-(3,4,5-trimethoxyphenyl)-4a,5,6,11b-tetrahydro-4H-[1,3]benzodioxolo[5,6-h][1,3]benzodioxine-5-carboxylate
  参考文献：
  名称：

  Lignopurines: A new family of hybrids between cyclolignans and purines. Synthesis and biological evaluation

  摘要：

  A new family of hybrids between cyclolignans related to podophyllic aldehyde, a non-lactonic cyclolignan, and purines were prepared and evaluated against several human tumour cell lines. Both fragments, cyclolignan and purine, were linked through aliphatic and aromatic chains. The influence on the cytotoxicity of the purine substitution and the nature of the linker is analyzed. The new family was slightly less cytotoxic than the parent podophyllic aldehyde, although the selectivity is maintained or even improved and among the linkers used, the presence of an aromatic ring gave the most potent and selective derivatives within the new series tested. Cell cycle and confocal studies demonstrate that these derivatives interfere with the tubulin polymerization and arrest cells at the G(2)/M phase, in the same way than the parent compounds podophyllotoxin and podophyllic aldehyde do. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.10.026

文献信息

• Improving Properties of Podophyllic Aldehyde-Derived Cyclolignans: Design, Synthesis and Evaluation of Novel Lignohydroquinones, Dual-Selective Hybrids against Colorectal Cancer Cells
  作者：Ángela-Patricia Hernández、Paula Díez、Pablo A. García、Martín Pérez-Andrés、Anzhela Veselinova、Pablo G. Jambrina、Arturo San Feliciano、David Díez、Manuel Fuentes、Mᵃ Ángeles Castro

  DOI：10.3390/pharmaceutics15030886

  日期：——

  New lignohydroquinone conjugates (L-HQs) were designed and synthesized using the hybridization strategy, and evaluated as cytotoxics against several cancer cell lines. The L-HQs were obtained from the natural product podophyllotoxin and some semisynthetic terpenylnaphthohydroquinones, prepared from natural terpenoids. Both entities of the conjugates were connected through different aliphatic or aromatic

  使用杂交策略设计和合成了新的木质素氢醌缀合物 (L-HQ)，并评估了对几种癌细胞系的细胞毒性。L-HQs 是从天然产物鬼臼毒素和一些由天然萜类化合物制备的半合成萜烯基萘氢醌中获得的。缀合物的两个实体通过不同的脂肪族或芳香族接头连接。在评估的杂交体中，带有芳香间隔基的 L-HQ 清楚地显示了来自每个起始成分的体外双重细胞毒性作用，保留了选择性并在短（24 小时）和长（72 小时）孵育时间显示出高细胞毒性（ 4.12 和 0.0450 µM，分别）对抗结直肠癌细胞。此外，通过流式细胞术研究、分子动力学、和微管蛋白相互作用研究证明了这种杂交体的兴趣，尽管它们的尺寸很大，但它们充分停靠在微管蛋白的秋水仙碱结合位点。这些结果证明了杂交策略的有效性，并鼓励对非内酯环木脂体的进一步研究。
• Lignopurines: A new family of hybrids between cyclolignans and purines. Synthesis and biological evaluation
  作者：Ma Ángeles Castro、José Ma. Miguel del Corral、Pablo A. García、Ma Victoria Rojo、Ana C. Bento、Faustino Mollinedo、Andrés M. Francesch、Arturo San Feliciano

  DOI：10.1016/j.ejmech.2012.10.026

  日期：2012.12

  A new family of hybrids between cyclolignans related to podophyllic aldehyde, a non-lactonic cyclolignan, and purines were prepared and evaluated against several human tumour cell lines. Both fragments, cyclolignan and purine, were linked through aliphatic and aromatic chains. The influence on the cytotoxicity of the purine substitution and the nature of the linker is analyzed. The new family was slightly less cytotoxic than the parent podophyllic aldehyde, although the selectivity is maintained or even improved and among the linkers used, the presence of an aromatic ring gave the most potent and selective derivatives within the new series tested. Cell cycle and confocal studies demonstrate that these derivatives interfere with the tubulin polymerization and arrest cells at the G(2)/M phase, in the same way than the parent compounds podophyllotoxin and podophyllic aldehyde do. (C) 2012 Elsevier Masson SAS. All rights reserved.