8-fluoro-5-trifluoromethanesulfonyloxy-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one | 1107631-28-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 8-fluoro-5-trifluoromethanesulfonyloxy-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one
• 英文别名: (8-Fluoro-2,2-dimethyl-4-oxo-1,3-benzodioxin-5-yl) trifluoromethanesulfonate
• CAS: 1107631-28-6
• 化学式: C₁₁H₈F₄O₆S
• 分子量: 344.241
• InChiKey: BOTBAGAPHPNPFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  87.3
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  8-fluoro-5-trifluoromethanesulfonyloxy-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one 、 烯丙基三丁基锡 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 三(2-呋喃基)膦 、 lithium chloride 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 8.0h， 以84%的产率得到8-fluoro-5-(2-propenyl)-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Fluorinated Analogues of Salicylihalamide

  摘要：

  Salicylihalamide A (SA), a benzolactone enamide compound, possesses potent cytotoxicity against human tumor cell lines. SA is a selective inhibitor of mammalian vacuolar type H+-ATPase (V-ATPase), and is distinct from previously known V-ATPase inhibitors such as bafilomycins and concanamycins that do not discriminate between mammalian and nonmammalian V-ATPases. Because of its potent antitumor activity and structural simplicity, SA is a promising candidate for an anticancer drug. Although a number of structure-activity relation studies using synthetic analogues have been reported, no fluorinated derivative of SA has been evaluated even though selective addition of a fluorine atom into a therapeutic small molecule candidate often enhances pharmacokinetic and physicochemical properties. We designed and synthesized fluorinated analogues of SA and evaluated their V-ATPase inhibitory activities. Compared to the natural product, the synthetic analogues were potent V-ATPase inhibitors, suggesting that these analogues are potential drug candidates and potential molecular probes for mode-of-action studies using fluorine-based analytical methods such as F-19-NMR spectroscopy.

  DOI：

  10.1021/jm801265e
• 作为产物：
  描述：

  三氟甲磺酸酐 、 8-Fluoro-5-hydroxy-2,2-dimethyl-1,3-benzodioxin-4-one 、 5-hydroxy-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one 以 吡啶 为溶剂， 反应 1.0h， 以1.07 g的产率得到8-fluoro-5-trifluoromethanesulfonyloxy-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Fluorinated Analogues of Salicylihalamide

  摘要：

  Salicylihalamide A (SA), a benzolactone enamide compound, possesses potent cytotoxicity against human tumor cell lines. SA is a selective inhibitor of mammalian vacuolar type H+-ATPase (V-ATPase), and is distinct from previously known V-ATPase inhibitors such as bafilomycins and concanamycins that do not discriminate between mammalian and nonmammalian V-ATPases. Because of its potent antitumor activity and structural simplicity, SA is a promising candidate for an anticancer drug. Although a number of structure-activity relation studies using synthetic analogues have been reported, no fluorinated derivative of SA has been evaluated even though selective addition of a fluorine atom into a therapeutic small molecule candidate often enhances pharmacokinetic and physicochemical properties. We designed and synthesized fluorinated analogues of SA and evaluated their V-ATPase inhibitory activities. Compared to the natural product, the synthetic analogues were potent V-ATPase inhibitors, suggesting that these analogues are potential drug candidates and potential molecular probes for mode-of-action studies using fluorine-based analytical methods such as F-19-NMR spectroscopy.

  DOI：

  10.1021/jm801265e