2-[(2R,3S,6R)-3-ethoxy-6-prop-2-enyl-3,6-dihydro-2H-pyran-2-yl]acetic acid | 1448680-48-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: 2-[(2R,3S,6R)-3-ethoxy-6-prop-2-enyl-3,6-dihydro-2H-pyran-2-yl]acetic acid
• CAS: 1448680-48-5
• 化学式: C₁₂H₁₈O₄
• 分子量: 226.273
• InChiKey: BMRFXCBOCHRGKG-OUAUKWLOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[(2R,3S,6R)-3-ethoxy-6-prop-2-enyl-3,6-dihydro-2H-pyran-2-yl]acetic acid 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 4-二甲氨基吡啶 、 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 22.0h， 生成 (1R,5S,8Z,11R,14S)-14-ethoxy-5-methyl-4,15-dioxabicyclo[9.3.1]pentadeca-8,12-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：

  (2R,3S,6R)-6-allyl-2-hydroxymethyl-3,6-dihydro-2H-pyran-3-ol 在 吡啶 、 sodium hydride 、 对甲苯磺酰氯 、 sodium hydroxide 作用下， 以 乙醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 16.0h， 生成 2-[(2R,3S,6R)-3-ethoxy-6-prop-2-enyl-3,6-dihydro-2H-pyran-2-yl]acetic acid
  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

文献信息

• Medicinal Chemistry of Dihydropyran-Based Medium Ring Macrolides Related to Aspergillides: Selective Inhibition of PI3Kα
  作者：Mallikharjuna R. Lambu、Suresh Kumar、Syed K. Yousuf、Deepak K. Sharma、Altaf Hussain、Ajay Kumar、Fayaz Malik、Debaraj Mukherjee

  DOI：10.1021/jm400515c

  日期：2013.8.8

  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.