(Z)-5-(2-hydroxyethyl)-3-[4-methyl-3-(methylethyl)pentylidene]-5-[(phenylmethoxy)methyl]-4,5-dihydrofuran-2-one | 663601-13-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (Z)-5-(2-hydroxyethyl)-3-[4-methyl-3-(methylethyl)pentylidene]-5-[(phenylmethoxy)methyl]-4,5-dihydrofuran-2-one
• CAS: 663601-13-6
• 化学式: C₂₃H₃₄O₄
• 分子量: 374.521
• InChiKey: UTCLUWXGWRHTSK-JMIUGGIZSA-N

物化性质

• 沸点：
  512.5±30.0 °C(Predicted)
• 密度：
  1.075±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.52
• 重原子数：
  27.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  55.76
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (Z)-5-(2-hydroxyethyl)-3-[4-methyl-3-(methylethyl)pentylidene]-5-[(phenylmethoxy)methyl]-4,5-dihydrofuran-2-one 在 sodium chlorite 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 、 草酰氯 、 二甲基亚砜 作用下， 以 二氯甲烷 、 叔丁醇 为溶剂， 反应 1.0h， 生成 (Z)-2-{4-[4-methyl-3-(methylethyl)pentylidene]-5-oxo-2-[(phenylmethoxy)methyl]-2-2,3-dihydrofuryl}acetic acid
  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：

  5-[(2,2-dimethyl-1,1-diphenyl-1-silapropoxy)methyl]-5-[(phenylmethoxy)methyl]-oxolan-2-ol 在 盐酸 、 二氯乙酸 、 四丙基高钌酸铵 、 dimethyl sulfide borane 、 4 A molecular sieve 、 DOWEX 50WX₈-200 、 potassium tert-butylate 、 四丁基氟化铵 、 sodium hydride 、 溶剂黄146 、 二甲基亚砜 、 N-甲基吗啉氧化物 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正庚烷 、 二氯甲烷 、 乙基苯 、 乙腈 为溶剂， 反应 117.0h， 生成 (Z)-5-(2-hydroxyethyl)-3-[4-methyl-3-(methylethyl)pentylidene]-5-[(phenylmethoxy)methyl]-4,5-dihydrofuran-2-one
  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