(E)-3-[4-[3-Isobutyl-5-methyl-hex-(Z)-ylidene]-2-(4-methoxy-phenoxymethyl)-5-oxo-tetrahydro-furan-2-yl]-acrylic acid tert-butyl ester | 924657-68-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (E)-3-[4-[3-Isobutyl-5-methyl-hex-(Z)-ylidene]-2-(4-methoxy-phenoxymethyl)-5-oxo-tetrahydro-furan-2-yl]-acrylic acid tert-butyl ester
• CAS: 924657-68-1
• 化学式: C₃₀H₄₄O₆
• 分子量: 500.676
• InChiKey: YDCUPSIPMIUCHD-VNIYWYTDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.68
• 重原子数：
  36.0
• 可旋转键数：
  12.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  71.06
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (E)-3-[4-[3-Isobutyl-5-methyl-hex-(Z)-ylidene]-2-(4-methoxy-phenoxymethyl)-5-oxo-tetrahydro-furan-2-yl]-acrylic acid tert-butyl ester 在 ammonium cerium(IV) nitrate 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以52%的产率得到(E)-3-{2-Hydroxymethyl-4-[3-isobutyl-5-methyl-hex-(Z)-ylidene]-5-oxo-tetrahydro-furan-2-yl}-acrylic acid tert-butyl ester
  参考文献：
  名称：

  Branched Diacylglycerol-Lactones as Potent Protein Kinase C Ligands and α-Secretase Activators

  摘要：

  Using as our lead structure a potent PKC ligand (1) that we had previously described, we investigated a series of branched DAG-lactones to optimize the scaffold for PKC binding affinity and reduced lipophilicity, and we examined the potential utility of select compounds as alpha-secretase activators. Activation of alpha-secretase upon PKC stimulation by ligands causes increased degradation of the amyloid precursor protein (APP), resulting in enhanced secretion of sAPP alpha and reduced deposition of beta-amyloid peptide (A beta), which is implicated in the pathogenesis of Alzheimer's disease. We modified in a systematic manner the C-5-acyl group, the 3-alkylidene, and the lactone ring in I and established structure-activity relationships for this series of potent PKC ligands. Select DAG-lactones with high binding affinities for PKC were evaluated for their abilities to lead to increased sAPP alpha secretion as a result of alpha-secretase activation. The DAG-lactones potently induced alpha-secretase activation, and their potencies correlated with the corresponding PKC binding affinities and lipophilicities. Further investigation indicated that 2 exhibited a modestly higher level of sAPP alpha secretion than did phorbol 12,13-dibutyrate (PDBu).

  DOI：

  10.1021/jm0509391
• 作为产物：
  描述：

  5-Benzyloxymethyl-3-(1-hydroxy-3-isobutyl-5-methyl-hexyl)-5-(4-methoxy-phenoxymethyl)-dihydro-furan-2-one 在 草酰氯 、 三氯化硼 、 二甲基亚砜 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 29.5h， 生成 (E)-3-[4-[3-Isobutyl-5-methyl-hex-(Z)-ylidene]-2-(4-methoxy-phenoxymethyl)-5-oxo-tetrahydro-furan-2-yl]-acrylic acid tert-butyl ester
  参考文献：
  名称：

  Branched Diacylglycerol-Lactones as Potent Protein Kinase C Ligands and α-Secretase Activators

  摘要：

  Using as our lead structure a potent PKC ligand (1) that we had previously described, we investigated a series of branched DAG-lactones to optimize the scaffold for PKC binding affinity and reduced lipophilicity, and we examined the potential utility of select compounds as alpha-secretase activators. Activation of alpha-secretase upon PKC stimulation by ligands causes increased degradation of the amyloid precursor protein (APP), resulting in enhanced secretion of sAPP alpha and reduced deposition of beta-amyloid peptide (A beta), which is implicated in the pathogenesis of Alzheimer's disease. We modified in a systematic manner the C-5-acyl group, the 3-alkylidene, and the lactone ring in I and established structure-activity relationships for this series of potent PKC ligands. Select DAG-lactones with high binding affinities for PKC were evaluated for their abilities to lead to increased sAPP alpha secretion as a result of alpha-secretase activation. The DAG-lactones potently induced alpha-secretase activation, and their potencies correlated with the corresponding PKC binding affinities and lipophilicities. Further investigation indicated that 2 exhibited a modestly higher level of sAPP alpha secretion than did phorbol 12,13-dibutyrate (PDBu).

  DOI：

  10.1021/jm0509391