ethyl (2E,4Z,6S)-6-methoxy-2-methyl-7-oxohepta-2,4-dienoate | 1225609-36-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl (2E,4Z,6S)-6-methoxy-2-methyl-7-oxohepta-2,4-dienoate
• CAS: 1225609-36-8
• 化学式: C₁₁H₁₆O₄
• 分子量: 212.246
• InChiKey: DNNJAUSXGGAHCD-RJPSNAOVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl (2E,4Z,6S)-6-methoxy-2-methyl-7-oxohepta-2,4-dienoate 在 四(三苯基膦)钯 、 1,3-二甲基巴比妥酸 、 叔丁基锂 作用下， 以 四氢呋喃 、 二氯甲烷 、 正戊烷 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  C15-甲氧基苯基化18-脱氧-草霉素A类似物，它们的体外抗癌活性和热休克蛋白90的结合亲和力。

  摘要：

  苯醌醌沙霉素是发现热休克蛋白90（Hsp90）新型抑制剂的重要线索，该抑制剂是癌症化学疗法的有希望的靶标。由苯醌部分引起的内在肝毒性似乎严重限制了这些化合物的开发。为了通过合理的结构优化来解决该问题，基于化合物与蛋白质之间的推定相互作用，设计了一系列除草霉素A的C18-脱氧类似物。通过遵循建立的天然产物合成路线来尝试化学合成目标分子，但最终分离出了四个偶然的C15苯基化的最终产物。测定了化合物的体外抗增殖活性和Hsp90结合亲和力，

  DOI：

  10.1016/j.bmcl.2016.07.040
• 作为产物：
  描述：

  (S,2E,4Z)-ethyl 7-hydroxy-6-methoxy-2-methylhepta-2,4-dienoate 在 2,2,6,6-四甲基哌啶氧化物 、 碘苯二乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 ethyl (2E,4Z,6S)-6-methoxy-2-methyl-7-oxohepta-2,4-dienoate
  参考文献：
  名称：

  Synthesis of Reblastatin, Autolytimycin, and Non-Benzoquinone Analogues: Potent Inhibitors of Heat Shock Protein 90

  摘要：

  A full account of an asymmetric synthesis of reblastatin (1) and the first total synthesis of autolytimycin (2) and related structural compounds is described. The syntheses expand the utility of a highly regio- and diastereoselective hydrometalation aldehyde addition sequence to assemble the fully functionalized ansa chain of the natural products. Also documented is an intramolecular copper-mediated amidation reaction to close the 19-membered macrolactams. The amidation reaction was also employed for the generation of structural derivatives (6-9) of phenolic ansamycins. Ansamycin natural products and selected structural analogues were evaluated in a competitive binding assay to breast cancer cell lysate and a cytotoxicity assay. Both reblastatin (1) and autolytimycin (2) were shown to bind the heat shock protein 90 with enhanced binding activity (similar to 25 nM) than 17-allylamino-17-demethoxygeldanamycin (17-AAG, 4), a geldanamycin (3) derivative currently under evaluation for treatment of cancer (similar to 100 nM).

  DOI：

  10.1021/jo1000109

文献信息

• Synthesis of Reblastatin, Autolytimycin, and Non-Benzoquinone Analogues: Potent Inhibitors of Heat Shock Protein 90
  作者：Iwona E. Wrona、Alexander Gozman、Tony Taldone、Gabriela Chiosis、James S. Panek

  DOI：10.1021/jo1000109

  日期：2010.5.7

  A full account of an asymmetric synthesis of reblastatin (1) and the first total synthesis of autolytimycin (2) and related structural compounds is described. The syntheses expand the utility of a highly regio- and diastereoselective hydrometalation aldehyde addition sequence to assemble the fully functionalized ansa chain of the natural products. Also documented is an intramolecular copper-mediated amidation reaction to close the 19-membered macrolactams. The amidation reaction was also employed for the generation of structural derivatives (6-9) of phenolic ansamycins. Ansamycin natural products and selected structural analogues were evaluated in a competitive binding assay to breast cancer cell lysate and a cytotoxicity assay. Both reblastatin (1) and autolytimycin (2) were shown to bind the heat shock protein 90 with enhanced binding activity (similar to 25 nM) than 17-allylamino-17-demethoxygeldanamycin (17-AAG, 4), a geldanamycin (3) derivative currently under evaluation for treatment of cancer (similar to 100 nM).
• C15-methoxyphenylated 18-deoxy-herbimycin A analogues, their in vitro anticancer activity and heat shock protein 90 binding affinity
  作者：Zhi Zhang、Nina Xue、Chuancai Bian、Rui Yan、Longlong Jin、Xiaoguang Chen、Xiaoming Yu

  DOI：10.1016/j.bmcl.2016.07.040

  日期：2016.9

  interactions between the compound and the protein. Chemical synthesis of the target molecules were attempted by following the established synthetic route to the natural product, but resulted in the isolation of four serendipitous C15 phenylated final products. In vitro antiproliferative activity and Hsp90 binding affinity of the compounds were determined, suggesting the C18-oxygen of herbimycin A is removable

  苯醌醌沙霉素是发现热休克蛋白90（Hsp90）新型抑制剂的重要线索，该抑制剂是癌症化学疗法的有希望的靶标。由苯醌部分引起的内在肝毒性似乎严重限制了这些化合物的开发。为了通过合理的结构优化来解决该问题，基于化合物与蛋白质之间的推定相互作用，设计了一系列除草霉素A的C18-脱氧类似物。通过遵循建立的天然产物合成路线来尝试化学合成目标分子，但最终分离出了四个偶然的C15苯基化的最终产物。测定了化合物的体外抗增殖活性和Hsp90结合亲和力，