2-(trimethylsilyl)ethyl 2-bromo-6-hydroxy-4-methoxybenzoate | 1071211-92-1

• 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: 2-(trimethylsilyl)ethyl 2-bromo-6-hydroxy-4-methoxybenzoate
• 英文别名: 2-Trimethylsilylethyl 2-bromo-6-hydroxy-4-methoxybenzoate
• CAS: 1071211-92-1
• 化学式: C₁₃H₁₉BrO₄Si
• 分子量: 347.281
• InChiKey: FMDHGJHACRSVGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.66
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(trimethylsilyl)ethyl 2-bromo-6-hydroxy-4-methoxybenzoate 、 (9R)-11,11-diethyl-9-methyl-5-(pent-4-en-1-yl)-2,4,10-trioxa-11-silatridec-6-yne 在 9-硼双环[3.3.1]壬烷 、 potassium phosphate 、 三(2-呋喃基)膦 、 palladium diacetate 作用下， 以 四氢呋喃 、 乙二醇二甲醚 为溶剂， 反应 2.5h， 以83%的产率得到2-(trimethylsilyl)ethyl 2-hydroxy-4-methoxy-6-((10R)-6-(methoxymethoxy)-10-((triethylsilyl)oxy)undec-7-yn-1-yl)benzoate
  参考文献：
  名称：

  Kinase Inhibition by Deoxy Analogues of the Resorcylic Lactone L-783277

  摘要：

  The natural product L-783277 is a resorcylic lactone type covalent kinase inhibitor We prepared the 5'-deoxy analogue of L-783277 (1) in a stereoselective fashion. Remarkably, this analogue retains almost the full kinase inhibitory potential of natural L-783277, with low nanomolar IC50 values against the most sensitive kinases, and it exhibits essentially the same selectivity profile (within the panel of 39 kinases investigated). In contrast, removal of both the 4'- and the 5'-hydroxyl groups leads to a more significant reduction in kinase inhibitory activity and so does a change in the geometry of the C7'-C8' double bond in 1 from Z to E. These findings offer new perspectives for the design of second generation resorcylic lactone-based kinase inhibitors.

  DOI：

  10.1021/ml1001807
• 作为产物：
  描述：

  2-(三甲硅基)乙醇 、 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以88%的产率得到2-(trimethylsilyl)ethyl 2-bromo-6-hydroxy-4-methoxybenzoate
  参考文献：
  名称：

  Total Synthesis of the Resorcylic Lactone-Based Kinase Inhibitor L-783277

  摘要：

  天然产物L-783277（1）的全合成基于模块9、10和14的汇聚式组装得以实现。关键步骤包括烯烃11与芳香模块14的Suzuki偶联、裂解酸16的基于Mitsunobu反应的大环内酯化，以及聚合物负载的IBX对大环三醇2的烯丙位氧化。仅有两种C6′立体异构体中的一种能够高选择性地提供L-783277（1）。

  DOI：

  10.1055/s-2008-1078406

文献信息

• Total Synthesis of the Resorcylic Lactone-Based Kinase Inhibitor L-783277
  作者：Karl-Heinz Altmann、Tatjana Hofmann

  DOI：10.1055/s-2008-1078406

  日期：2008.6

  The total synthesis of the natural product L-783277 (1) has been accomplished based on the convergent assembly of building blocks 9, 10, and 14. Key steps are the Suzuki coupling of olefin 11 and aromatic building block 14, the Mitsunobu-based macrolactonization of seco acid 16, and the allylic oxidation of the macrocyclic triol 2 with polymer-bound IBX. Only one of the two C6′-stereoisomers of 2 provided L-783277 (1) with high selectivity.

  天然产物L-783277（1）的全合成基于模块9、10和14的汇聚式组装得以实现。关键步骤包括烯烃11与芳香模块14的Suzuki偶联、裂解酸16的基于Mitsunobu反应的大环内酯化，以及聚合物负载的IBX对大环三醇2的烯丙位氧化。仅有两种C6′立体异构体中的一种能够高选择性地提供L-783277（1）。
• Kinase Inhibition by Deoxy Analogues of the Resorcylic Lactone L-783277
  作者：Marc Liniger、Christian Neuhaus、Tatjana Hofmann、Luca Fransioli-Ignazio、Michel Jordi、Peter Drueckes、Jörg Trappe、Doriano Fabbro、Karl-Heinz Altmann

  DOI：10.1021/ml1001807

  日期：2011.1.13

  The natural product L-783277 is a resorcylic lactone type covalent kinase inhibitor We prepared the 5'-deoxy analogue of L-783277 (1) in a stereoselective fashion. Remarkably, this analogue retains almost the full kinase inhibitory potential of natural L-783277, with low nanomolar IC50 values against the most sensitive kinases, and it exhibits essentially the same selectivity profile (within the panel of 39 kinases investigated). In contrast, removal of both the 4'- and the 5'-hydroxyl groups leads to a more significant reduction in kinase inhibitory activity and so does a change in the geometry of the C7'-C8' double bond in 1 from Z to E. These findings offer new perspectives for the design of second generation resorcylic lactone-based kinase inhibitors.