(R)-3-(tert-butyldimethylsilyloxy)tetradec-13-ynal | 1204939-43-4

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: (R)-3-(tert-butyldimethylsilyloxy)tetradec-13-ynal
• CAS: 1204939-43-4
• 化学式: C₂₀H₃₈O₂Si
• 分子量: 338.606
• InChiKey: RLYGKGJLONSKFF-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.11
• 重原子数：
  23.0
• 可旋转键数：
  13.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  26.3
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (R)-3-(tert-butyldimethylsilyloxy)tetradec-13-ynal 、 (E)-2-(1-(tert-butyldimethylsilyloxy)oct-1-enylthio)pyridine 在 zinc(II) chloride 作用下， 以 二氯甲烷 为溶剂， 反应 72.0h， 生成 、
  参考文献：
  名称：

  Activity-Based Proteome Profiling of Potential Cellular Targets of Orlistat − An FDA-Approved Drug with Anti-Tumor Activities

  摘要：

  Orlistat, or tetrahydrolipstatin (THL), is an FDA-approved antiobesity drug with potential antitumor activities. Cellular off-targets and potential side effects of Orlistat in cancer therapies, however, have not been extensively explored thus far. In this study, we report the total of synthesis of THL-like protein-reactive probes, in which extremely conservative modifications (i.e., an alkyne handle) were introduced in the parental THL structure to maintain the native biological properties of Orlistat, while providing the necessary functionality for target identification via the bio-orthogonal click chemistry. With these natural productlike, cell-permeable probes, we were able to demonstrate, for the first time, this chemical proteomic approach is suitable for the identification of previously unknown cellular targets of Orlistat. In addition to the expected fatty acid synthase (FAS), we identified a total of eight new targets, some of which were further validated by experiments including Western blotting, recombinant protein expression, and site-directed mutagenesis. Our findings have important implications in the consideration of Orlistat as a potential anticancer drug at its early stages of development for cancer therapy. Our strategy should be broadly useful for off-target identification against quite a number of existing drugs and/or candidates, which are also covalent modifiers of their biological targets.

  DOI：

  10.1021/ja907716f
• 作为产物：
  描述：

  (R)-tert-butyldimethyl(pentadec-1-en-14-yn-4-yloxy)silane 在 臭氧 、 三乙胺 、 二甲基硫 作用下， 以 二氯甲烷 为溶剂， 以80%的产率得到(R)-3-(tert-butyldimethylsilyloxy)tetradec-13-ynal
  参考文献：
  名称：

  Activity-Based Proteome Profiling of Potential Cellular Targets of Orlistat − An FDA-Approved Drug with Anti-Tumor Activities

  摘要：

  Orlistat, or tetrahydrolipstatin (THL), is an FDA-approved antiobesity drug with potential antitumor activities. Cellular off-targets and potential side effects of Orlistat in cancer therapies, however, have not been extensively explored thus far. In this study, we report the total of synthesis of THL-like protein-reactive probes, in which extremely conservative modifications (i.e., an alkyne handle) were introduced in the parental THL structure to maintain the native biological properties of Orlistat, while providing the necessary functionality for target identification via the bio-orthogonal click chemistry. With these natural productlike, cell-permeable probes, we were able to demonstrate, for the first time, this chemical proteomic approach is suitable for the identification of previously unknown cellular targets of Orlistat. In addition to the expected fatty acid synthase (FAS), we identified a total of eight new targets, some of which were further validated by experiments including Western blotting, recombinant protein expression, and site-directed mutagenesis. Our findings have important implications in the consideration of Orlistat as a potential anticancer drug at its early stages of development for cancer therapy. Our strategy should be broadly useful for off-target identification against quite a number of existing drugs and/or candidates, which are also covalent modifiers of their biological targets.

  DOI：

  10.1021/ja907716f