2,2-Dimethyl-propionic acid 5-[3-isobutyl-5-methyl-hex-(Z)-ylidene]-2-(4-methoxy-phenoxymethyl)-6-oxo-tetrahydro-pyran-2-ylmethyl ester | 924658-92-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 2,2-Dimethyl-propionic acid 5-[3-isobutyl-5-methyl-hex-(Z)-ylidene]-2-(4-methoxy-phenoxymethyl)-6-oxo-tetrahydro-pyran-2-ylmethyl ester
• CAS: 924658-92-4
• 化学式: C₃₀H₄₆O₆
• 分子量: 502.692
• InChiKey: RTCAJXNXSXVXJS-VROXFSQNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.76
• 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：
  0.67
• 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：

  2,2-Dimethyl-propionic acid 5-[3-isobutyl-5-methyl-hex-(Z)-ylidene]-2-(4-methoxy-phenoxymethyl)-6-oxo-tetrahydro-pyran-2-ylmethyl ester 在 ammonium cerium(IV) nitrate 作用下， 以 乙腈 为溶剂， 反应 0.5h， 以76%的产率得到6-hydroxymethyl-3-[(Z)-3-isobutyl-5-methylhexylidene]-6-pivaloyloxymethyl-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 4-二甲氨基吡啶 、 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 57.5h， 生成 2,2-Dimethyl-propionic acid 5-[3-isobutyl-5-methyl-hex-(Z)-ylidene]-2-(4-methoxy-phenoxymethyl)-6-oxo-tetrahydro-pyran-2-ylmethyl 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