(E)-3-{4-[4-methyl-3-(methylethyl)pentylidene]-5-oxo-2-[(phenylmethoxy)methyl]-2-2,3-dihydrofuryl}propyl octanoate | 663601-34-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-3-{4-[4-methyl-3-(methylethyl)pentylidene]-5-oxo-2-[(phenylmethoxy)methyl]-2-2,3-dihydrofuryl}propyl octanoate
• CAS: 663601-34-1
• 化学式: C₃₂H₅₀O₅
• 分子量: 514.746
• InChiKey: SICDHDDVQLCMBT-MTDXEUNCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.82
• 重原子数：
  37.0
• 可旋转键数：
  18.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  61.83
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (E)-3-{4-[4-methyl-3-(methylethyl)pentylidene]-5-oxo-2-[(phenylmethoxy)methyl]-2-2,3-dihydrofuryl}propyl octanoate 在 三氯化硼 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以93%的产率得到3-[(4E)-2-(hydroxymethyl)-4-(4-methyl-3-propan-2-ylpentylidene)-5-oxooxolan-2-yl]propyl octanoate
  参考文献：
  名称：

  Conformationally Constrained Analogues of Diacylglycerol. 20. The Search for an Elusive Binding Site on Protein Kinase C through Relocation of the Carbonyl Pharmacophore Along the sn-1 Side Chain of 1,2-Diacylglycerol Lactones

  摘要：

  Previous studies with 1,2-diacylglycerol (DAG) lactones, which behave as high-affinity ligands for protein kinase C (PK-C), have established the importance of maintaining intact the pharmacophore triad of two carbonyl moieties (sn-1 and sn-2) and the primary alcohol. In addition, docking studies of DAG-lactones into an empty C1b receptor of PK-Cdelta (as it appears in complex with phorbol 13-O-acetate) have revealed that in either of the two possible binding alternatives (sn-1 or sn-2) only one carbonyl group of the DAG-lactone is involved in binding. Therefore, the unknown receptor for the orphaned carbonyl appears to lie outside the boundaries of this binary complex, possibly residing at the membrane or near the membrane-protein interface. A strategy to locate the optimal location of the unengaged carbonyl was conceived by utilizing a small group of DAG-lactones (1-4) with a highly branched chain adjacent to the sn-2 carbonyl such that sn-2 binding is favored. With these compounds, various locations of the sn-1 carbonyl along the side chain were tested for their binding affinity for PK-C. The results indicate that the location of the side chain sn-1 carbonyl in a DAG-lactone must have perfect mimicry to the sn-1 carbonyl of the parent DAG for it to display high binding affinity. A proposed model from this work is that the missing pharmacophore in the ternary complex, which includes the membrane, is close to the membrane-protein interface.

  DOI：

  10.1021/jm030454h
• 作为产物：
  描述：

  (E)-5-{3-[(4-methoxyphenyl)methoxy]propyl}-3-[4-methyl-3-(methylethyl)pentylidene]-5-[(phenylmethoxy)methyl]-4,5-dihydrofuran-2-one 在 吡啶 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 生成 (E)-3-{4-[4-methyl-3-(methylethyl)pentylidene]-5-oxo-2-[(phenylmethoxy)methyl]-2-2,3-dihydrofuryl}propyl octanoate
  参考文献：
  名称：

  Conformationally Constrained Analogues of Diacylglycerol. 20. The Search for an Elusive Binding Site on Protein Kinase C through Relocation of the Carbonyl Pharmacophore Along the sn-1 Side Chain of 1,2-Diacylglycerol Lactones

  摘要：

  Previous studies with 1,2-diacylglycerol (DAG) lactones, which behave as high-affinity ligands for protein kinase C (PK-C), have established the importance of maintaining intact the pharmacophore triad of two carbonyl moieties (sn-1 and sn-2) and the primary alcohol. In addition, docking studies of DAG-lactones into an empty C1b receptor of PK-Cdelta (as it appears in complex with phorbol 13-O-acetate) have revealed that in either of the two possible binding alternatives (sn-1 or sn-2) only one carbonyl group of the DAG-lactone is involved in binding. Therefore, the unknown receptor for the orphaned carbonyl appears to lie outside the boundaries of this binary complex, possibly residing at the membrane or near the membrane-protein interface. A strategy to locate the optimal location of the unengaged carbonyl was conceived by utilizing a small group of DAG-lactones (1-4) with a highly branched chain adjacent to the sn-2 carbonyl such that sn-2 binding is favored. With these compounds, various locations of the sn-1 carbonyl along the side chain were tested for their binding affinity for PK-C. The results indicate that the location of the side chain sn-1 carbonyl in a DAG-lactone must have perfect mimicry to the sn-1 carbonyl of the parent DAG for it to display high binding affinity. A proposed model from this work is that the missing pharmacophore in the ternary complex, which includes the membrane, is close to the membrane-protein interface.

  DOI：

  10.1021/jm030454h