methyl (E)‐4‐(4‐acetoxystyryl)benzoate | 1242050-75-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: methyl (E)‐4‐(4‐acetoxystyryl)benzoate
• 英文别名: methyl 4-[(E)-2-(4-acetyloxyphenyl)ethenyl]benzoate
• CAS: 1242050-75-4
• 化学式: C₁₈H₁₆O₄
• 分子量: 296.323
• InChiKey: DKPALFPEVSEOAH-ONEGZZNKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 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 (E)‐4‐(4‐acetoxystyryl)benzoate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 以34 %的产率得到4'-hydroxy-trans-stilbene-4-carboxylic acid
  参考文献：
  名称：

  What doesn't fit is made to fit: Pim‐1 kinase adapts to the configuration of stilbene‐based inhibitors

  摘要：

  Recently, we have developed novel Pim‐1 kinase inhibitors starting from a dihydrobenzofuran core structure using a computational approach. Here, we report the design and synthesis of stilbene‐based Pim‐1 kinase inhibitors obtained by formal elimination of the dihydrofuran ring. These inhibitors of the first design cycle, which were obtained as inseparable cis/trans mixtures, showed affinities in the low single‐digit micromolar range. To be able to further optimize these compounds in a structure‐based fashion, we determined the X‐ray structures of the protein‐ligand‐complexes. Surprisingly, only the cis‐isomer binds upon crystallization of the cis/trans‐mixture of the ligands with Pim‐1 kinase and the substrate PIMTIDE, the binding mode being largely consistent with that predicted by docking. After crystallization of the exclusively trans‐configured derivatives, a markedly different binding mode for the inhibitor and a concomitant rearrangement of the glycine‐rich loop is observed, resulting in the ligand being deeply buried in the binding pocket.

  DOI：

  10.1002/ardp.202400094
• 作为产物：
  描述：

  4-溴甲基苯甲酸甲酯 在 potassium tert-butylate 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 3.5h， 生成 methyl (E)‐4‐(4‐acetoxystyryl)benzoate
  参考文献：
  名称：

  What doesn't fit is made to fit: Pim‐1 kinase adapts to the configuration of stilbene‐based inhibitors

  摘要：

  Recently, we have developed novel Pim‐1 kinase inhibitors starting from a dihydrobenzofuran core structure using a computational approach. Here, we report the design and synthesis of stilbene‐based Pim‐1 kinase inhibitors obtained by formal elimination of the dihydrofuran ring. These inhibitors of the first design cycle, which were obtained as inseparable cis/trans mixtures, showed affinities in the low single‐digit micromolar range. To be able to further optimize these compounds in a structure‐based fashion, we determined the X‐ray structures of the protein‐ligand‐complexes. Surprisingly, only the cis‐isomer binds upon crystallization of the cis/trans‐mixture of the ligands with Pim‐1 kinase and the substrate PIMTIDE, the binding mode being largely consistent with that predicted by docking. After crystallization of the exclusively trans‐configured derivatives, a markedly different binding mode for the inhibitor and a concomitant rearrangement of the glycine‐rich loop is observed, resulting in the ligand being deeply buried in the binding pocket.

  DOI：

  10.1002/ardp.202400094

文献信息

• Unravelling the olefin cross metathesis on solid support. Factors affecting the reaction outcome
  作者：Andrés A. Poeylaut-Palena、Ernesto G. Mata

  DOI：10.1039/c004729e

  日期：——

  Olefin cross metathesis on solid support under a variety of conditions is described. A comprehensive analysis considering diverse factors governing the reaction outcome gives a series of patterns for the application of this useful methodology in organic synthesis. If the intrasite reaction is not possible, homodimerization of the soluble olefin is crucial. When the homodimer is less reactive than its monomer, reaction outcome depends on the homodimerization rate, which, in turn, depends on the precatalyst used and the reaction conditions. If the site–site interaction is a feasible process, the cross metathesis product is obtained exclusively when the newly-formed double bond is resilient to further metathetic events. Taking into account these considerations, we have demonstrated that excellent results in terms of cross metathesis coupling can be obtained under the optimized conditions, and that microwave irradiation is also an interesting alternative for the development of a practical and energy-efficient cross metathesis on solid support.

  描述了在多种条件下固体支持上的烯烃交叉致密反应。对影响反应结果的各种因素进行综合分析，提供了一系列模式，便于在有机合成中应用这一有用的方法论。如果站点内反应不可行，溶解烯烃的同聚化至关重要。当同聚物的反应性低于其单体时，反应结果取决于同聚化速率，而这又取决于所使用的前催化剂和反应条件。如果站点间相互作用是可行的过程，当新形成的双键对进一步的致密反应具有抵抗力时，将独占性地获得交叉致密产物。考虑到这些因素，我们展示了在优化条件下可以获得交叉致密耦合的优秀结果，并且微波辐射也是开发实用且节能的固体支持交叉致密反应的一个有趣选择。