6-hydroxymethyl-3-[(E)-3-isobutyl-5-methylhexylidene]-6-[(4-methoxyphenoxy)methyl]tetrahydro-2-pyranone | 881850-46-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 6-hydroxymethyl-3-[(E)-3-isobutyl-5-methylhexylidene]-6-[(4-methoxyphenoxy)methyl]tetrahydro-2-pyranone
• 英文别名: (3E)-6-(hydroxymethyl)-6-[(4-methoxyphenoxy)methyl]-3-[5-methyl-3-(2-methylpropyl)hexylidene]oxan-2-one
• CAS: 881850-46-0
• 化学式: C₂₅H₃₈O₅
• 分子量: 418.574
• InChiKey: JNKVPNWSXHQSSD-QPSGOUHRSA-N

物化性质

• 沸点：
  566.2±30.0 °C(Predicted)
• 密度：
  1.069±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-hydroxymethyl-3-[(E)-3-isobutyl-5-methylhexylidene]-6-[(4-methoxyphenoxy)methyl]tetrahydro-2-pyranone 在 4-二甲氨基吡啶 、 ammonium cerium(IV) nitrate 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 3.5h， 生成 6-hydroxymethyl-3-[(E)-3-isobutyl-5-methylhexylidene]-6-hexanoyloxymethyl-tetrahydro-2-pyranone
  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：

  tert-butyl 4-{[(4-methoxyphenoxy)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl}butanoate 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 54.5h， 生成 6-hydroxymethyl-3-[(E)-3-isobutyl-5-methylhexylidene]-6-[(4-methoxyphenoxy)methyl]tetrahydro-2-pyranone
  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