5-(benzyloxy)methyl-3-[(E)-12-carboxyundecylidene]-5-hydroxymethyltetrahydro-2-furanone | 745073-44-3

• 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: 5-(benzyloxy)methyl-3-[(E)-12-carboxyundecylidene]-5-hydroxymethyltetrahydro-2-furanone
• 英文别名: (12E)-12-[5-(hydroxymethyl)-2-oxo-5-(phenylmethoxymethyl)oxolan-3-ylidene]dodecanoic acid
• CAS: 745073-44-3
• 化学式: C₂₅H₃₆O₆
• 分子量: 432.557
• InChiKey: MUIXNHPVQVWMJU-PXLXIMEGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  31
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-(benzyloxy)methyl-3-[(E)-12-carboxyundecylidene]-5-hydroxymethyltetrahydro-2-furanone 在 4-二甲氨基吡啶 、 4-(dimethylamino)pyridine hydrochloride 、 三氯化硼 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 1-hydroxymethyl-3,18-dioxabicyclo[14.2.1]nonadec-15(E)-ene-4,17-dione
  参考文献：
  名称：

  Macrocyclic Diacylglycerol-bis-lactones as Conformationally Constrained Analogues of Diacylglycerol-lactones. Interactions with Protein Kinase C

  摘要：

  A series of macrocyclic diacylglycerol (DAG)-bis-lactones were investigated as extreme conformationally constrained analogues of DAG-lactones in order to seek more potent protein kinase C (PKC) ligands with higher binding affinities and less lipophilicity than previous compounds. The additional constraint achieved the desired objective as exemplified by the macrocyclic DAG-bis-lactone 57, which exhibited a 6-fold higher binding affinity for PKCalpha (K-i = 6.07 nM) than the corresponding nonmacrocyclic 3-alkylidene DAG-lactone 6. A structure-activity relationship (SAR) analysis of the macrocyclic DAG-bis-lactones demonstrated a parabolic relationship between activity and lipophilicity, as well as a predilection for the Z-alkylidene isomers as the preferred ligands. Molecular docking studies revealed that macrocyclic DAG-bis-lactone 57 bound to the C1b domain of PKCalpha exclusively in the sn-1 binding mode in contrast to DAG-lactone 6, which showed both sn-1 and sn-2 binding modes. It is proposed that the high potency displayed by these macrocyclic DAG-bis-lactones results from a set of more favorable hydrogen bonding and hydrophobic interactions with PKCalpha as well as from a reduced entropy penalty due to conformational restriction.

  DOI：

  10.1021/jm0497747
• 作为产物：
  描述：

  1,12-十二烷二醇 在 吡啶 、 重铬酸吡啶 、 甲酸 、 ammonium cerium(IV) nitrate 、 pyridinium chloroformate 、 4 A molecular sieve 、 甲基磺酰氯 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 35.0h， 生成 5-(benzyloxy)methyl-3-[(E)-12-carboxyundecylidene]-5-hydroxymethyltetrahydro-2-furanone
  参考文献：
  名称：

  Macrocyclic Diacylglycerol-bis-lactones as Conformationally Constrained Analogues of Diacylglycerol-lactones. Interactions with Protein Kinase C

  摘要：

  A series of macrocyclic diacylglycerol (DAG)-bis-lactones were investigated as extreme conformationally constrained analogues of DAG-lactones in order to seek more potent protein kinase C (PKC) ligands with higher binding affinities and less lipophilicity than previous compounds. The additional constraint achieved the desired objective as exemplified by the macrocyclic DAG-bis-lactone 57, which exhibited a 6-fold higher binding affinity for PKCalpha (K-i = 6.07 nM) than the corresponding nonmacrocyclic 3-alkylidene DAG-lactone 6. A structure-activity relationship (SAR) analysis of the macrocyclic DAG-bis-lactones demonstrated a parabolic relationship between activity and lipophilicity, as well as a predilection for the Z-alkylidene isomers as the preferred ligands. Molecular docking studies revealed that macrocyclic DAG-bis-lactone 57 bound to the C1b domain of PKCalpha exclusively in the sn-1 binding mode in contrast to DAG-lactone 6, which showed both sn-1 and sn-2 binding modes. It is proposed that the high potency displayed by these macrocyclic DAG-bis-lactones results from a set of more favorable hydrogen bonding and hydrophobic interactions with PKCalpha as well as from a reduced entropy penalty due to conformational restriction.

  DOI：

  10.1021/jm0497747