(5S,6S)-6-[(1E,3R,4R,6R,7Z)-6-(tert-butyldimethylsilyloxy)-4-hydroxy-8-iodo-3-methyl-3-(triethylsilyloxy)-octa-1,7-dien-1-yl]-5-(4-(2-[2-(prop-2-yn-1-yloxy)ethoxy]ethoxy)benzyloxy)-5,6-dihydro-2H-pyran-2-one | 1204085-40-4

• 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: (5S,6S)-6-[(1E,3R,4R,6R,7Z)-6-(tert-butyldimethylsilyloxy)-4-hydroxy-8-iodo-3-methyl-3-(triethylsilyloxy)-octa-1,7-dien-1-yl]-5-(4-(2-[2-(prop-2-yn-1-yloxy)ethoxy]ethoxy)benzyloxy)-5,6-dihydro-2H-pyran-2-one
• CAS: 1204085-40-4
• 化学式: C₄₀H₆₃IO₉Si₂
• 分子量: 871.01
• InChiKey: PTHXNBPAKZBAEB-PJYJJWMYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.53
• 重原子数：
  52.0
• 可旋转键数：
  24.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  101.91
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  N-[2-(2-叠氮基乙氧基)乙基]-5-[(3aS,4S,6aR)-2-氧代六氢-1H-噻吩并[3,4-d]咪唑-4-基]戊酰胺 、 (5S,6S)-6-[(1E,3R,4R,6R,7Z)-6-(tert-butyldimethylsilyloxy)-4-hydroxy-8-iodo-3-methyl-3-(triethylsilyloxy)-octa-1,7-dien-1-yl]-5-(4-(2-[2-(prop-2-yn-1-yloxy)ethoxy]ethoxy)benzyloxy)-5,6-dihydro-2H-pyran-2-one 在 copper(l) iodide 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.33h， 以98%的产率得到N-(2-[2-(4-([2-(2-(4-[(((2S,3S)-2-[(1E,3R,4R,6R,7Z)-6-(tert-butyldimethylsilyloxy)-4-hydroxy-8-iodo-3-methyl-3-(triethylsilyloxy)-octa-1,7-dien-1-yl]-6-oxo-3,6-dihydro-2H-pyran-3-yl)oxy)methyl]phenoxy)ethoxy)ethoxy]methyl)-1H-1,2,3-triazol-1-yl)ethoxy]ethyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide
  参考文献：
  名称：

  Antitumor antibiotic fostriecin covalently binds to cysteine-269 residue of protein phosphatase 2A catalytic subunit in mammalian cells

  摘要：

  Fostriecin is a phosphate monoester with excellent antitumor activity against mouse leukemia, and it is a potent inhibitor of protein phosphatase (PP) 2A. This compound has been predicted to covalently bind to the Cys269 residue of the PP2A catalytic subunit (PP2Ac) at the alpha,beta-unsaturated lactone via a conjugate addition reaction. However, this binding has not yet been experimentally proven. To confirm such binding, we synthesized biotin-labeled fostriecin (bio-Fos), which has an inhibitory activity against the proliferation of mouse leukemia cells. We showed that fostriecin directly binds to PP2Ac in HeLa S3 cells by pull-down assays using bio-Fos. Moreover, we directly demonstrated that fostriecin covalently binds to the Cys269 residue of PP2Ac by matrix assisted laser desorption/ionization time-of-flight mass spectrometry analysis. From these results, the inhibitory mechanism of fostriecin on PP2A activity is discussed. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.09.050
• 作为产物：
  描述：

  在 盐酸 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 2.5h， 以36 mg的产率得到(5S,6S)-6-[(1E,3R,4R,6R,7Z)-6-(tert-butyldimethylsilyloxy)-4-hydroxy-8-iodo-3-methyl-3-(triethylsilyloxy)-octa-1,7-dien-1-yl]-5-(4-(2-[2-(prop-2-yn-1-yloxy)ethoxy]ethoxy)benzyloxy)-5,6-dihydro-2H-pyran-2-one
  参考文献：
  名称：

  Antitumor antibiotic fostriecin covalently binds to cysteine-269 residue of protein phosphatase 2A catalytic subunit in mammalian cells

  摘要：

  Fostriecin is a phosphate monoester with excellent antitumor activity against mouse leukemia, and it is a potent inhibitor of protein phosphatase (PP) 2A. This compound has been predicted to covalently bind to the Cys269 residue of the PP2A catalytic subunit (PP2Ac) at the alpha,beta-unsaturated lactone via a conjugate addition reaction. However, this binding has not yet been experimentally proven. To confirm such binding, we synthesized biotin-labeled fostriecin (bio-Fos), which has an inhibitory activity against the proliferation of mouse leukemia cells. We showed that fostriecin directly binds to PP2Ac in HeLa S3 cells by pull-down assays using bio-Fos. Moreover, we directly demonstrated that fostriecin covalently binds to the Cys269 residue of PP2Ac by matrix assisted laser desorption/ionization time-of-flight mass spectrometry analysis. From these results, the inhibitory mechanism of fostriecin on PP2A activity is discussed. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.09.050