| 1033754-88-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 甘油磷脂
• CAS: 1033754-88-9
• 化学式: C₆₇H₈₄O₁₅P₂
• 分子量: 1191.34
• InChiKey: AARNAGMBNLKDPC-BRVSGQTHSA-N

物化性质

• 沸点：
  1050.6±65.0 °C(predicted)
• 密度：
  1.22±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  15.98
• 重原子数：
  84.0
• 可旋转键数：
  40.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  169.81
• 氢给体数：
  0.0
• 氢受体数：
  15.0

反应信息

• 作为反应物：
  描述：

  在 palladium dihydroxide 氢气 作用下， 以 水 、 叔丁醇 为溶剂， 反应 32.0h， 生成
  参考文献：
  名称：

  Insights into the Structural Specificity of the Cytotoxicity of 3-Deoxyphosphatidylinositols

  摘要：

  D-3-Deoxyphosphatidylinositol (D-3-deoxy-PI) derivatives have cytotoxic activity against various human cancer cell lines. These phosphatidylinositols have a potentially wide array of targets in the phosphatidylinositol-3-kinase (PI3K)/Akt signaling network. To explore the specificity of these types of molecules, we have synthesized D-3-deoxydioctanoylphosphatidylinositol (D-3-deoxy-diC(8)PI), D-3,5-dideoxydiC(8)PI, and D-3-deoxy-diC(8)PI-5-phosphate and their enantiomers, characterized their aggregate formation by novel high-resolution field cycling P-31 NMR, and examined their susceptibility to phospholipase C (PLC), their effects on the catalytic activities of PI3K and PTEN against diC(8)PI and diC(8)PI-3-phosphate substrates, respectively, and their ability to induce the death of U937 human leukemic monocyte lymphoma cells. Of these molecules, only D-3-cleoxy-diC(8)PI was able to promote cell death; it did so with a median inhibitory concentration of 40 mu M, which is much less than the critical micelle concentration of 0.4 mM. Under these conditions, little inhibition of PI3K or PTEN was observed in assays of recombinant enzymes, although the complete series of deoxy-PI compounds did provide insights into ligand binding by PTEN. D-3-DeoxydiC(8)PI was a poor substrate and not an inhibitor of the PLC enzymes. The in vivo results are consistent with the current thought that the PI analogue acts on Akt1, since the transcription initiation factor eIF4e, which is a downstream signaling target of the PI3K/Akt pathway, exhibited reduced phosphorylation on Ser209. Phosphorylation of Akt1 on Ser473 but not Thr308 was reduced. Since the potent cytotoxicity for U937 cells was completely lost when L-3-deoxy-diC(8)PI was used as well as when the hydroxyl group at the inositol C5 in D-3-deoxy-diC(8)PI was modified (by either replacing this group with a hydrogen or phosphorylating it), both the chirality of the phosphatidylinositol moiety and the hydroxyl group at C5 are major determinants of the binding of 3-deoxy-PI to its target in cells.

  DOI：

  10.1021/ja710348r
• 作为产物：
  描述：

  C₆₇H₈₄O₁₄P₂ 在 双氧水 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Insights into the Structural Specificity of the Cytotoxicity of 3-Deoxyphosphatidylinositols

  摘要：

  D-3-Deoxyphosphatidylinositol (D-3-deoxy-PI) derivatives have cytotoxic activity against various human cancer cell lines. These phosphatidylinositols have a potentially wide array of targets in the phosphatidylinositol-3-kinase (PI3K)/Akt signaling network. To explore the specificity of these types of molecules, we have synthesized D-3-deoxydioctanoylphosphatidylinositol (D-3-deoxy-diC(8)PI), D-3,5-dideoxydiC(8)PI, and D-3-deoxy-diC(8)PI-5-phosphate and their enantiomers, characterized their aggregate formation by novel high-resolution field cycling P-31 NMR, and examined their susceptibility to phospholipase C (PLC), their effects on the catalytic activities of PI3K and PTEN against diC(8)PI and diC(8)PI-3-phosphate substrates, respectively, and their ability to induce the death of U937 human leukemic monocyte lymphoma cells. Of these molecules, only D-3-cleoxy-diC(8)PI was able to promote cell death; it did so with a median inhibitory concentration of 40 mu M, which is much less than the critical micelle concentration of 0.4 mM. Under these conditions, little inhibition of PI3K or PTEN was observed in assays of recombinant enzymes, although the complete series of deoxy-PI compounds did provide insights into ligand binding by PTEN. D-3-DeoxydiC(8)PI was a poor substrate and not an inhibitor of the PLC enzymes. The in vivo results are consistent with the current thought that the PI analogue acts on Akt1, since the transcription initiation factor eIF4e, which is a downstream signaling target of the PI3K/Akt pathway, exhibited reduced phosphorylation on Ser209. Phosphorylation of Akt1 on Ser473 but not Thr308 was reduced. Since the potent cytotoxicity for U937 cells was completely lost when L-3-deoxy-diC(8)PI was used as well as when the hydroxyl group at the inositol C5 in D-3-deoxy-diC(8)PI was modified (by either replacing this group with a hydrogen or phosphorylating it), both the chirality of the phosphatidylinositol moiety and the hydroxyl group at C5 are major determinants of the binding of 3-deoxy-PI to its target in cells.

  DOI：

  10.1021/ja710348r