((E)-2-(hydroxymethyl)-4-((9Z,12Z)-octadeca-9,12-dien-1-ylidene)-5 oxotetrahydrofuran-2-yl)methyl pivalate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: ((E)-2-(hydroxymethyl)-4-((9Z,12Z)-octadeca-9,12-dien-1-ylidene)-5 oxotetrahydrofuran-2-yl)methyl pivalate
• 英文别名: [(4E)-2-(hydroxymethyl)-4-[(9Z,12Z)-octadeca-9,12-dienylidene]-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate
• 化学式: C₂₉H₄₈O₅
• 分子量: 476.697
• InChiKey: VANSLOBMJZSUSD-ZHWZMQKBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.4
• 重原子数：
  34
• 可旋转键数：
  19
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  亚油酸甲酯 在 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 ammonium cerium (IV) nitrate 、 草酰氯 、 三氯化硼 、 二甲基亚砜 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 3.5h， 生成 ((E)-2-(hydroxymethyl)-4-((9Z,12Z)-octadeca-9,12-dien-1-ylidene)-5 oxotetrahydrofuran-2-yl)methyl pivalate
  参考文献：
  名称：

  Design and synthesis of protein kinase C epsilon selective diacylglycerol lactones (DAG-lactones)

  摘要：

  DAG-lactones afford a synthetically accessible, high affinity platform for probing structure activity relationships at the Cl regulatory domain of protein kinase C (PKC). Given the central role of PKC isoforms in cellular signaling, along with their differential biological activities, a critical objective is the design of isoform selective ligands. Here, we report the synthesis of a series of DAG-lactones varying in their side chains, with a particular focus on linoleic acid derivatives. We evaluated their selectivity for PKC epsilon versus PKC alpha both under standard lipid conditions (100% phosphatidylserine, PS) as well as in the presence of a nuclear membrane mimetic lipid mixture (NML). We find that selectivity for PKC epsilon versus PKC alpha tended to be enhanced in the presence of the nuclear membrane mimetic lipid mixture and, for our lead compound, report a selectivity of 32-fold. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.11.025

文献信息

• Design and synthesis of protein kinase C epsilon selective diacylglycerol lactones (DAG-lactones)
  作者：Jihyae Ann、Suyoung Yoon、Jisoo Baek、Da Hye Kim、Nancy E. Lewin、Colin S. Hill、Peter M. Blumberg、Jeewoo Lee

  DOI：10.1016/j.ejmech.2014.11.025

  日期：2015.1

  DAG-lactones afford a synthetically accessible, high affinity platform for probing structure activity relationships at the Cl regulatory domain of protein kinase C (PKC). Given the central role of PKC isoforms in cellular signaling, along with their differential biological activities, a critical objective is the design of isoform selective ligands. Here, we report the synthesis of a series of DAG-lactones varying in their side chains, with a particular focus on linoleic acid derivatives. We evaluated their selectivity for PKC epsilon versus PKC alpha both under standard lipid conditions (100% phosphatidylserine, PS) as well as in the presence of a nuclear membrane mimetic lipid mixture (NML). We find that selectivity for PKC epsilon versus PKC alpha tended to be enhanced in the presence of the nuclear membrane mimetic lipid mixture and, for our lead compound, report a selectivity of 32-fold. (C) 2014 Elsevier Masson SAS. All rights reserved.