(E)-{2-(hydroxymethyl)-4-[5-methyl-3-(2-methylpropyl)hyxylidene]-5-thioxo-2-2,3-dihydrofuryl}methyl 2,2-dimethylpropanoate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧唑烯
• 英文名称: (E)-{2-(hydroxymethyl)-4-[5-methyl-3-(2-methylpropyl)hyxylidene]-5-thioxo-2-2,3-dihydrofuryl}methyl 2,2-dimethylpropanoate
• 英文别名: [(4E)-2-(hydroxymethyl)-4-[5-methyl-3-(2-methylpropyl)hexylidene]-5-sulfanylideneoxolan-2-yl]methyl 2,2-dimethylpropanoate
• 化学式: C₂₂H₃₈O₄S
• 分子量: 398.607
• InChiKey: WEAXGDQVWHPARP-GIJQJNRQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  27
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  87.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  二异丁基酮 在 palladium on activated charcoal 劳森试剂 、 4 A molecular sieve 、 氢气 、 三溴化硼 、 甲基磺酰氯 、 三乙胺 、 pyridinium chlorochromate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 47.42h， 生成 (E)-{2-(hydroxymethyl)-4-[5-methyl-3-(2-methylpropyl)hyxylidene]-5-thioxo-2-2,3-dihydrofuryl}methyl 2,2-dimethylpropanoate
  参考文献：
  名称：

  Conformationally Constrained Analogues of Diacylglycerol (DAG). 25. Exploration of the sn-1 and sn-2 Carbonyl Functionality Reveals the Essential Role of the sn-1 Carbonyl at the Lipid Interface in the Binding of DAG-Lactones to Protein Kinase C

  摘要：

  Diacylglycerol (DAG) lactones with altered functionality (C=O -> CH2 or C=O -> C=S) at the sn-1 and sn-2 carbonyl pharmacophores were synthesized and used as probes to dissect the individual role of each carbonyl in the binding to protein kinase C (PKC). The results suggest that the hydrated sn-1 carbonyl is engaged in very strong hydrogen-bonding interactions with the charged lipid headgroups and organized water molecules at the lipid interface. Conversely, the sn-2 carbonyl has a more modest contribution to the binding process as a result of its involvement with the receptor (Cl domain) via conventional hydrogen bonding to the protein. The parent DAG-lactones, E-6 and Z-7, were designed to bind exclusively in the sn-2 binding mode to ensure the correct orientation and disposition of pharmacophores at the binding site.

  DOI：

  10.1021/jm050352m

文献信息

• Conformationally Constrained Analogues of Diacylglycerol (DAG). 25. Exploration of the <i>sn</i>-1 and <i>sn</i>-2 Carbonyl Functionality Reveals the Essential Role of the <i>sn</i>-1 Carbonyl at the Lipid Interface in the Binding of DAG-Lactones to Protein Kinase C
  作者：Ji-Hye Kang、Megan L. Peach、Yongmei Pu、Nancy E. Lewin、Marc C. Nicklaus、Peter M. Blumberg、Victor E. Marquez

  DOI：10.1021/jm050352m

  日期：2005.9.1

  Diacylglycerol (DAG) lactones with altered functionality (C=O -> CH2 or C=O -> C=S) at the sn-1 and sn-2 carbonyl pharmacophores were synthesized and used as probes to dissect the individual role of each carbonyl in the binding to protein kinase C (PKC). The results suggest that the hydrated sn-1 carbonyl is engaged in very strong hydrogen-bonding interactions with the charged lipid headgroups and organized water molecules at the lipid interface. Conversely, the sn-2 carbonyl has a more modest contribution to the binding process as a result of its involvement with the receptor (Cl domain) via conventional hydrogen bonding to the protein. The parent DAG-lactones, E-6 and Z-7, were designed to bind exclusively in the sn-2 binding mode to ensure the correct orientation and disposition of pharmacophores at the binding site.