methyl (2Z,4E,6S,7S)-7-[tert-butyl(dimethyl)silyl]oxy-6-methyl-9-oxonona-2,4-dienoate | 1075200-47-3

• 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: methyl (2Z,4E,6S,7S)-7-[tert-butyl(dimethyl)silyl]oxy-6-methyl-9-oxonona-2,4-dienoate
• CAS: 1075200-47-3
• 化学式: C₁₇H₃₀O₄Si
• 分子量: 326.508
• InChiKey: TXYXVKDOSQSXQO-BDOYQWIGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.89
• 重原子数：
  22
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.65
• 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：

  methyl (2Z,4E,6S,7S)-7-[tert-butyl(dimethyl)silyl]oxy-6-methyl-9-oxonona-2,4-dienoate 、 乙烯基溴化镁 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 (2Z,4E,6S,7S,9RS)-methyl 7-(tert-butyldimethylsilyloxy)-9-hydroxy-6-methylundeca-2,4,10-trienoate
  参考文献：
  名称：

  Improved Synthesis of 6-epi-Dictyostatin and Antitumor Efficacy in Mice Bearing MDA-MB231 Human Breast Cancer Xenografts

  摘要：

  Structure-activity Studies centered oil the naturally occurring antitumor agent dictyostatin have recently identified several highly active epimers and analogues. From these compounds, 6-epi-dictyostatin was selected for scaleup preparation and evaluation in animals. Here we describe a new total synthesis that produced more than 30 mg of 6-epi-diclyostatin. The compound was found to have potent antitumor activity in SCID mice bearing MDA-MB231 human breast cancer xenografts.

  DOI：

  10.1021/jm800979v
• 作为产物：
  描述：

  在 戴斯-马丁氧化剂 作用下， 生成 methyl (2Z,4E,6S,7S)-7-[tert-butyl(dimethyl)silyl]oxy-6-methyl-9-oxonona-2,4-dienoate
  参考文献：
  名称：

  Improved Synthesis of 6-epi-Dictyostatin and Antitumor Efficacy in Mice Bearing MDA-MB231 Human Breast Cancer Xenografts

  摘要：

  Structure-activity Studies centered oil the naturally occurring antitumor agent dictyostatin have recently identified several highly active epimers and analogues. From these compounds, 6-epi-dictyostatin was selected for scaleup preparation and evaluation in animals. Here we describe a new total synthesis that produced more than 30 mg of 6-epi-diclyostatin. The compound was found to have potent antitumor activity in SCID mice bearing MDA-MB231 human breast cancer xenografts.

  DOI：

  10.1021/jm800979v

文献信息

• Streamlined Syntheses of (−)-Dictyostatin, 16-Desmethyl-25,26-dihydrodictyostatin, and 6-<i>epi</i>-16-Desmethyl-25,26-dihydrodictyostatin
  作者：Wei Zhu、María Jiménez、Won-Hyuk Jung、Daniel P. Camarco、Raghavan Balachandran、Andreas Vogt、Billy W. Day、Dennis P. Curran

  DOI：10.1021/ja103537u

  日期：2010.7.7

  provide a third new synthesis based on esterification and Nozaki-Hiyama-Kishi reaction. This was used to prepare the target dihydro analogues and the natural product. All of the syntheses are streamlined because of their high convergency. The work provided several new analogues of dictyostatin, including a truncated macrolactone and a C10 E-alkene, which were 400- and 50-fold less active than (-)-dictyostatin

  dictyostatins 是一类很有前景的潜在抗癌药物，因为它们是强大的微管稳定剂，但其化学结构的复杂性严重阻碍了它们的进一步发展。在合成和药物化学分析的基础上，16-desmethyl-25,26-dihydrodictyostatin 及其 C6 差向异构体被选为潜在有效但可用的 dictyostatin 类似物，并开发了三种新的合成方法。涉及乙烯基锂加成和大环化的相对经典的合成让位于基于酯化和闭环复分解反应的更新和更实用的方法。最后，结合这两种方法的各个方面以提供基于酯化和 Nozaki-Hiyama-Kishi 反应的第三种新合成。这用于制备目标二氢类似物和天然产物。由于它们的高收敛性，所有的合成都是流线型的。这项工作提供了几种新的 dictyostatin 类似物，包括截短的大环内酯和 C10 E-烯烃，它们的活性分别比 (-)-dictyostatin 低 400 和 50 倍。相比之下，靶向