(Z)-5,5-bis(hydroxymethyl)-3-[4-methyl-3-(methylethyl)pentylidene]-4,5-dihydrofuran-2-one | 261357-31-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (Z)-5,5-bis(hydroxymethyl)-3-[4-methyl-3-(methylethyl)pentylidene]-4,5-dihydrofuran-2-one
• 英文别名: (3Z)-5,5-bis(hydroxymethyl)-3-(4-methyl-3-propan-2-ylpentylidene)oxolan-2-one
• CAS: 261357-31-7
• 化学式: C₁₅H₂₆O₄
• 分子量: 270.369
• InChiKey: PGCBFZGUHNTZME-XGICHPGQSA-N

物化性质

• 沸点：
  419.5±30.0 °C(Predicted)
• 密度：
  1.100±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  间甲氧基苯甲酰氯 、 (Z)-5,5-bis(hydroxymethyl)-3-[4-methyl-3-(methylethyl)pentylidene]-4,5-dihydrofuran-2-one 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以57%的产率得到[(4Z)-2-(hydroxymethyl)-4-(4-methyl-3-propan-2-ylpentylidene)-5-oxooxolan-2-yl]methyl 3-methoxybenzoate
  参考文献：
  名称：

  Conformationally Constrained Analogues of Diacylglycerol. 26. Exploring the Chemical Space Surrounding the C1 Domain of Protein Kinase C with DAG-Lactones Containing Aryl Groups at the sn-1 and sn-2 Positions

  摘要：

  Diacylglycerol lactones (DAG-lactones) are known to operate as effective agonists of protein kinase C (PKC), surpassing in potency the activity of natural diacylglycerol (DAG). Localization of activated PKC isozymes in the cell is determined in part by the different cellular scaffolds, the lipid composition of the specific membranes, and the targeting information intrinsic to the individual isoforms bound to DAG. This multifaceted control of diversity suggests that, to develop effective DAG-lactones capable of honing in on a specific cellular target, we need to gain a better understanding of the chemical space surrounding its binding site. Seeking to augment the chemical repertoire of DAG-lactone side chains that could steer the translocation of PKC to specific cellular domains, we report herein the effects of incorporating simple or substituted phenyl residues. A combined series of n-alkyl and phenyl substitutions were used to explore the optimal location of the phenyl group on the side chains. The substantial differences in binding affinity between DAG-lactones with identical functionalized phenyl groups at either the sn-1 or sn-2 position are consistent with the proposed binding model in which the DAG-lactone binds to the C1 domain of PKC with the acyl chain oriented toward the interior of the membrane and the alpha-alkylidene or alpha-arylalkylidene chains directed to the surface of the C1 domain adjacent to the lipid interface. We conclude that DAG-lactones containing alpha-phenylalkylidene side chains at the sn-2 position represent excellent scaffolds upon which to explore further chemical diversity.

  DOI：

  10.1021/jm060011o
• 作为产物：
  描述：

  (Z)-5,5-bis[(2,2-dimethyl-1,1-diphenyl-1-silapropoxy)methyl]-3-[4-methyl-3-(methylethyl)pentylidene]-4,5-dihydrofuran-2-one 在 吡啶 、 氢氟酸 作用下， 以 二氯甲烷 为溶剂， 生成 (Z)-5,5-bis(hydroxymethyl)-3-[4-methyl-3-(methylethyl)pentylidene]-4,5-dihydrofuran-2-one
  参考文献：
  名称：

  Differential Binding Modes of Diacylglycerol (DAG) and DAG Lactones to Protein Kinase C (PK-C)

  摘要：

  Diacylglycerol lactones (DAG lactones), analogous to highly potent diacylglycerols (DAGs) were synthesized to demonstrate the ability of PK-C to discriminate between two differential binding modes, sn-1 and sn-2. While both sn-1 and sn-2 binding modes are allowable in terms of hydrogen bonding, it has been found that in general, DAGs prefer to bind sn-1, while the corresponding analogous DAG lactones prefer to bind sn-2. However, this binding orientation can be directly influenced by the disposition and nature of the acyl substituent, particularly if it is highly branched. When the "binding driving force" (i.e., the larger branched acyl chain) is in the sn-2 position, a dramatic increase in binding affinity is observed in the DAG lactone as compared to its open chain DAG counterpart. As these analogous DAGs and DAG lactones have almost identical log P values, this difference in binding affinity is a direct result of the entropic advantage of constraining the glycerol backbone.

  DOI：

  10.1021/jm020476o

文献信息

• Conformationally Constrained Analogues of Diacylglycerol. 26. Exploring the Chemical Space Surrounding the C1 Domain of Protein Kinase C with DAG-Lactones Containing Aryl Groups at the <i>sn</i>-1 and <i>sn</i>-2 Positions
  作者：Ji-Hye Kang、Samira Benzaria、Dina M. Sigano、Nancy E. Lewin、Yongmei Pu、Megan L. Peach、Peter M. Blumberg、Victor E. Marquez

  DOI：10.1021/jm060011o

  日期：2006.6.1

  Diacylglycerol lactones (DAG-lactones) are known to operate as effective agonists of protein kinase C (PKC), surpassing in potency the activity of natural diacylglycerol (DAG). Localization of activated PKC isozymes in the cell is determined in part by the different cellular scaffolds, the lipid composition of the specific membranes, and the targeting information intrinsic to the individual isoforms bound to DAG. This multifaceted control of diversity suggests that, to develop effective DAG-lactones capable of honing in on a specific cellular target, we need to gain a better understanding of the chemical space surrounding its binding site. Seeking to augment the chemical repertoire of DAG-lactone side chains that could steer the translocation of PKC to specific cellular domains, we report herein the effects of incorporating simple or substituted phenyl residues. A combined series of n-alkyl and phenyl substitutions were used to explore the optimal location of the phenyl group on the side chains. The substantial differences in binding affinity between DAG-lactones with identical functionalized phenyl groups at either the sn-1 or sn-2 position are consistent with the proposed binding model in which the DAG-lactone binds to the C1 domain of PKC with the acyl chain oriented toward the interior of the membrane and the alpha-alkylidene or alpha-arylalkylidene chains directed to the surface of the C1 domain adjacent to the lipid interface. We conclude that DAG-lactones containing alpha-phenylalkylidene side chains at the sn-2 position represent excellent scaffolds upon which to explore further chemical diversity.
• Differential Binding Modes of Diacylglycerol (DAG) and DAG Lactones to Protein Kinase C (PK-C)
  作者：Dina M. Sigano、Megan L. Peach、Kassoum Nacro、Yongseok Choi、Nancy E. Lewin、Marc C. Nicklaus、Peter M. Blumberg、Victor E. Marquez

  DOI：10.1021/jm020476o

  日期：2003.4.1

  Diacylglycerol lactones (DAG lactones), analogous to highly potent diacylglycerols (DAGs) were synthesized to demonstrate the ability of PK-C to discriminate between two differential binding modes, sn-1 and sn-2. While both sn-1 and sn-2 binding modes are allowable in terms of hydrogen bonding, it has been found that in general, DAGs prefer to bind sn-1, while the corresponding analogous DAG lactones prefer to bind sn-2. However, this binding orientation can be directly influenced by the disposition and nature of the acyl substituent, particularly if it is highly branched. When the "binding driving force" (i.e., the larger branched acyl chain) is in the sn-2 position, a dramatic increase in binding affinity is observed in the DAG lactone as compared to its open chain DAG counterpart. As these analogous DAGs and DAG lactones have almost identical log P values, this difference in binding affinity is a direct result of the entropic advantage of constraining the glycerol backbone.