6,8-二溴-4-氧代-4H-1-苯并吡喃-3-甲醛 | 25088-82-8

• 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
• 中文名称: 6,8-二溴-4-氧代-4H-1-苯并吡喃-3-甲醛
• 英文名称: 9-deoxyanhydropodophyllol
• 英文别名: (5aR)-5t-(3,4,5-trimethoxy-phenyl)-(5ar,8at)-5,5a,6,8,8a,9-hexahydro-furo[3',4';6,7]naphtho[2,3-d][1,3]dioxole；(5aR)-5t-(3,4,5-Trimethoxy-phenyl)-(5ar,8at)-5,5a,6,8,8a,9-hexahydro-furo[3',4';6,7]naphtho[2,3-d][1,3]dioxol；5,5a,6,8,8a,9-Hexahydro-5-(3,4,5-trimethoxyphenyl)furo(3',4':6,7)naphtho(2,3-d)-1,3-dioxole stereoisomer；(5R,5aR,8aR)-5-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9-hexahydro-[2]benzofuro[5,6-f][1,3]benzodioxole
• CAS: 25088-82-8
• 化学式: C₂₂H₂₄O₆
• 分子量: 384.429
• InChiKey: CKUGPDQJERTFDI-WDUKFBBWSA-N

物化性质

• 沸点：
  501.8±50.0 °C(Predicted)
• 密度：
  1.244±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  55.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6,8-二溴-4-氧代-4H-1-苯并吡喃-3-甲醛 在 葡萄糖 、 recombinant human cytochrome P₄₅₀ 3A₄ 、 还原型辅酶II(NADPH)四钠盐 作用下， 以 phosphate buffer 、 二甲基亚砜 为溶剂， 反应 0.33h， 生成 (5S,5aR,8aR,9R)-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9-hexahydro-[2]benzofuro[5,6-f][1,3]benzodioxol-5-ol
  参考文献：
  名称：

  Metabolic stereoselectivity of cytochrome P450 3A4 towards deoxypodophyllotoxin: In silico predictions and experimental validation

  摘要：

  Deoxypodophyllotoxin is stereoselectively converted into epipodophyllotoxin by recombinant human cytochrome P450 3A4 (CY-P3A4). Further kinetic analysis revealed that the Michaelis-Menten K(m) and V(max) for hydroxylation of deoxypodophyllotoxin by CYP3A4 at C7 position were 1.93 mu M and 1.48 nmol/min/nmol, respectively. Deoxypodophyllotoxin was subjected to automated docking analysis in order to get better knowledge of the interaction between the CYP3A4 enzyme and the substrate, using the PatchDock algorithm with distance constraints. Automated docking showed that the P-hydrogen atom at C7 position is in the most appropriate binding orientation at the site of oxidation. The docking results are consistent with the experimental data for the bioconversion of deoxypodophyllotoxin into epipodophyllotoxin by CYP3A4. In addition, the effects of five lignans, deoxypodophyllotoxin, epipodophyllotoxin, podophyllotoxin, demethylenedeoxypodophyllotoxin, and demethylenepodophyllotoxin, on CYP3A4 were compared in order to investigate the influence of the methylenedioxy group on the biotransformation process, to give insight into the mode of metabolization and to explain inhibitory activity of lignans. (c) 2007 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2007.09.005
• 作为产物：
  描述：

  去氧鬼臼毒素 在 吡啶 、 lithium aluminium tetrahydride 、 对甲苯磺酰氯 作用下， 反应 3.0h， 生成 6,8-二溴-4-氧代-4H-1-苯并吡喃-3-甲醛
  参考文献：
  名称：

  Cytotoxic Responses to Aromatic Ring and Configurational Variations in α-Conidendrin, Podophyllotoxin, and Sikkimotoxin Derivatives

  摘要：

  Derivatives of alpha -conidendrin, podophyllotoxin, and sikkimotoxin were prepared to evaluate the cytotoxic contributions of C-4 configuration and pendant and fused arene substitutions. Dimethyl-alpha -conidendryl alcohol (5), 9-deoxypodophyllol (6), and 9-deoxysikkimol (17) were dehydrated to their respective oxolane derivatives 4, 3, and 9. Diols 5 and 6 were converted via oxabicyclo[3.2.1] octanols 10 and 14 to target oxolanes 8 and 7 where C-4 had been inverted relative to that in 3 and 4. Cytotoxicities of the five oxolanes were determined in two drug-sensitive human leukemia and two multidrug-resistant cell lines expressing P-glycoprotein or multidrug-resistance associated protein (MRP). Changing the pendant arene configuration or replacing a m-methoxy by hydrogen resulted in a 100-fold cytotoxicity loss. Replacing a methylenedioxy group in the fused arene by two methoxy substituents reduced cytotoxicity by 10-fold. Drug-resistant cell lines were equally resistant to compounds 3, 4, 8, and 9 indicating that these four compounds do not serve as substrates of the transport proteins P-glycoprotein and MRP.

  DOI：

  10.1021/jm990563p

文献信息

• Application of Tosylate Reductions and Molecular Rotations to the Stereochemistry of Lignans²
  作者：Anthony W. Schrecker、Jonathan L. Hartwell

  DOI：10.1021/ja01607a063

  日期：1955.1
• ——
  作者：TAKANO SEHJITI、 OGASAVARA KOKURO、 OTAKI SIDZUO

  DOI：——

  日期：——
• Cytotoxic Responses to Aromatic Ring and Configurational Variations in α-Conidendrin, Podophyllotoxin, and Sikkimotoxin Derivatives
  作者：Anne Dantzig、Robert T. LaLonde、Frank Ramdayal、Robert L. Shepard、Koichi Yanai、Mianji Zhang

  DOI：10.1021/jm990563p

  日期：2001.1.1

  Derivatives of alpha -conidendrin, podophyllotoxin, and sikkimotoxin were prepared to evaluate the cytotoxic contributions of C-4 configuration and pendant and fused arene substitutions. Dimethyl-alpha -conidendryl alcohol (5), 9-deoxypodophyllol (6), and 9-deoxysikkimol (17) were dehydrated to their respective oxolane derivatives 4, 3, and 9. Diols 5 and 6 were converted via oxabicyclo[3.2.1] octanols 10 and 14 to target oxolanes 8 and 7 where C-4 had been inverted relative to that in 3 and 4. Cytotoxicities of the five oxolanes were determined in two drug-sensitive human leukemia and two multidrug-resistant cell lines expressing P-glycoprotein or multidrug-resistance associated protein (MRP). Changing the pendant arene configuration or replacing a m-methoxy by hydrogen resulted in a 100-fold cytotoxicity loss. Replacing a methylenedioxy group in the fused arene by two methoxy substituents reduced cytotoxicity by 10-fold. Drug-resistant cell lines were equally resistant to compounds 3, 4, 8, and 9 indicating that these four compounds do not serve as substrates of the transport proteins P-glycoprotein and MRP.
• Metabolic stereoselectivity of cytochrome P450 3A4 towards deoxypodophyllotoxin: In silico predictions and experimental validation
  作者：Mattijs K. Julsing、Nikolay P. Vasilev、Dina Schneidman-Duhovny、Remco Muntendam、Herman J. Woerdenbag、Wim J. Quax、Haim J. Wolfson、Iliana Ionkova、Oliver Kayser

  DOI：10.1016/j.ejmech.2007.09.005

  日期：2008.6

  Deoxypodophyllotoxin is stereoselectively converted into epipodophyllotoxin by recombinant human cytochrome P450 3A4 (CY-P3A4). Further kinetic analysis revealed that the Michaelis-Menten K(m) and V(max) for hydroxylation of deoxypodophyllotoxin by CYP3A4 at C7 position were 1.93 mu M and 1.48 nmol/min/nmol, respectively. Deoxypodophyllotoxin was subjected to automated docking analysis in order to get better knowledge of the interaction between the CYP3A4 enzyme and the substrate, using the PatchDock algorithm with distance constraints. Automated docking showed that the P-hydrogen atom at C7 position is in the most appropriate binding orientation at the site of oxidation. The docking results are consistent with the experimental data for the bioconversion of deoxypodophyllotoxin into epipodophyllotoxin by CYP3A4. In addition, the effects of five lignans, deoxypodophyllotoxin, epipodophyllotoxin, podophyllotoxin, demethylenedeoxypodophyllotoxin, and demethylenepodophyllotoxin, on CYP3A4 were compared in order to investigate the influence of the methylenedioxy group on the biotransformation process, to give insight into the mode of metabolization and to explain inhibitory activity of lignans. (c) 2007 Elsevier Masson SAS. All rights reserved.