1-(4-fluorophenyl)but-3-en-1-yl 2-((2R,3S,6R)-6-allyl-3-((4-methoxybenzyl)oxy)-3,6-dihydro-2H-pyran-2-yl)acetate | 1448680-59-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(4-fluorophenyl)but-3-en-1-yl 2-((2R,3S,6R)-6-allyl-3-((4-methoxybenzyl)oxy)-3,6-dihydro-2H-pyran-2-yl)acetate
• CAS: 1448680-59-8
• 化学式: C₂₈H₃₁FO₅
• 分子量: 466.55
• InChiKey: KRYCAHBVNHGXBZ-VSYPSCETSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.87
• 重原子数：
  34.0
• 可旋转键数：
  12.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  53.99
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  1-(4-fluorophenyl)but-3-en-1-yl 2-((2R,3S,6R)-6-allyl-3-((4-methoxybenzyl)oxy)-3,6-dihydro-2H-pyran-2-yl)acetate 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 以41%的产率得到(1R,5R,7Z,10R,13S)-5-(4-fluorophenyl)-13-[(4-methoxyphenyl)methoxy]-4,14-dioxabicyclo[8.3.1]tetradeca-7,11-dien-3-one
  参考文献：
  名称：

  Medicinal Chemistry of Dihydropyran-Based Medium Ring Macrolides Related to Aspergillides: Selective Inhibition of PI3Kα

  摘要：

  A set of nine trans-disubstituted dihydropyran-based medium ring macrolides has been synthesized using D-glucal as chiral pool and evaluated against a panel of three human cancer cell lines and a normal cell line. The synthetic route to the targeted molecule is simple, concise, and high yielding compared to other reported methods. Bioevaluation studies have resulted in the identification of a potent cytotoxic molecule (10) exhibiting dose-dependent growth inhibition against HL-60 cell line with an IC50 value of 1.10 +/- 0.075 mu M, which is lower than that of naturally occurring molecules of this class and of comparable activity to the synthetic drug fludarubin. Compound 10 inhibits the PI3K/AKT signaling pathway by selectively targeting the p110 alpha subunit of PI3K alpha. This leads to mitochondrial stress that causes translocation of cytochrome c from mitochondria to cytosol, which in turn activates caspase-mediated apoptotic cell death. Further in silico docking simulations of four macrolides with p110 alpha subunits have been carried out to visualize the orientation pattern.

  DOI：

  10.1021/jm400515c
• 作为产物：
  描述：

  对氟苯甲醛 在 4-二甲氨基吡啶 、 iron(III) chloride 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 14.0h， 生成 1-(4-fluorophenyl)but-3-en-1-yl 2-((2R,3S,6R)-6-allyl-3-((4-methoxybenzyl)oxy)-3,6-dihydro-2H-pyran-2-yl)acetate
  参考文献：
  名称：

  Medicinal Chemistry of Dihydropyran-Based Medium Ring Macrolides Related to Aspergillides: Selective Inhibition of PI3Kα

  摘要：

  A set of nine trans-disubstituted dihydropyran-based medium ring macrolides has been synthesized using D-glucal as chiral pool and evaluated against a panel of three human cancer cell lines and a normal cell line. The synthetic route to the targeted molecule is simple, concise, and high yielding compared to other reported methods. Bioevaluation studies have resulted in the identification of a potent cytotoxic molecule (10) exhibiting dose-dependent growth inhibition against HL-60 cell line with an IC50 value of 1.10 +/- 0.075 mu M, which is lower than that of naturally occurring molecules of this class and of comparable activity to the synthetic drug fludarubin. Compound 10 inhibits the PI3K/AKT signaling pathway by selectively targeting the p110 alpha subunit of PI3K alpha. This leads to mitochondrial stress that causes translocation of cytochrome c from mitochondria to cytosol, which in turn activates caspase-mediated apoptotic cell death. Further in silico docking simulations of four macrolides with p110 alpha subunits have been carried out to visualize the orientation pattern.

  DOI：

  10.1021/jm400515c