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 | 1204085-53-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 生物素及其衍生物
• 英文名称: 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
• CAS: 1204085-53-9
• 化学式: C₅₄H₈₇IN₆O₁₂SSi₂
• 分子量: 1227.46
• InChiKey: SFCCMZXLQDDGFH-ANOMYJDZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.54
• 重原子数：
  76.0
• 可旋转键数：
  36.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  212.08
• 氢给体数：
  4.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  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 、 (1Z,3E)-5-tert-butyldiphenylsilyloxy-1-tributylstannylpenta-1,3-diene 在 双(乙腈)氯化钯(II) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 以81%的产率得到N-(2-[2-(4-([2-(2-(4-[(((2S,3S)-2-[(1E,3R,4R,6R,7Z,9Z,11E)-6-(tert-butyldimethylsilyloxy)-13-(tert-butyldiphenylsilyloxy)-4-hydroxy-3-methyl-3-(triethylsilyloxy)-trideca-1,7,9,11-tetraen-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：

  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