2,4,6-tri-O-benzyl-5-O-tert-butyldimethylsilyl-D-myo-inositol-3-deoxy-1-dibenzyl phosphate | 899827-39-5

• 英文名称: 2,4,6-tri-O-benzyl-5-O-tert-butyldimethylsilyl-D-myo-inositol-3-deoxy-1-dibenzyl phosphate
• 英文别名: dibenzyl [(1R,2R,3S,4R,6R)-3-[tert-butyl(dimethyl)silyl]oxy-2,4,6-tris(phenylmethoxy)cyclohexyl] phosphate
• CAS: 899827-39-5
• 化学式: C₄₇H₅₇O₈PSi
• 分子量: 809.024
• InChiKey: NLUMPAFKRLGAQE-FYAIVFOGSA-N

物化性质

• 沸点：
  793.0±60.0 °C(predicted)
• 密度：
  1.17±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  11.46
• 重原子数：
  57
• 可旋转键数：
  20
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  81.7
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2,4,6-tri-O-benzyl-5-O-tert-butyldimethylsilyl-D-myo-inositol-3-deoxy-1-dibenzyl phosphate 在 氟化氢吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 48.0h， 以75%的产率得到2,4,6-tri-O-benzyl-D-myo-inositol-3-deoxy-1-dibenzyl phosphate
  参考文献：
  名称：

  简化的磷脂酰肌醇（PI），PI3P，PI3,5P 2和脱氧类似物的合成作为潜在的生物探针

  摘要：

  据报道，磷脂酰肌醇（PI），磷脂酰肌醇-3-磷酸酯（PI3P），磷脂酰肌醇-3,5-双磷酸酯（PI3,5P 2）和一系列脱氧形式的高度直接的全合成。进行每个合成以递送光学纯形式的靶标。对于每个合成中的关键步骤是催化不对称磷酸化反应，影响适当的desymmetrization肌醇-肌醇的前体。然后采用通用前体的面向多样性的策略对每种目标化合物进行精细加工。除三种天然产物外，还报道了几种其他简化的脱氧PI类似物的总合成方法。这些合成为这些膜相关信号分子的极性头基/生物靶标相互作用的高精度生物学研究奠定了基础。

  DOI：

  10.1021/jo060702s
• 作为产物：
  描述：

  1-O-diphenylphosphate-2,4,6-tri-O-benzyl-D-myo-inositol 在 吡啶 、 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 偶氮二异丁腈 、 三正丁基氢锡 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 10.0h， 生成 2,4,6-tri-O-benzyl-5-O-tert-butyldimethylsilyl-D-myo-inositol-3-deoxy-1-dibenzyl phosphate
  参考文献：
  名称：

  简化的磷脂酰肌醇（PI），PI3P，PI3,5P 2和脱氧类似物的合成作为潜在的生物探针

  摘要：

  据报道，磷脂酰肌醇（PI），磷脂酰肌醇-3-磷酸酯（PI3P），磷脂酰肌醇-3,5-双磷酸酯（PI3,5P 2）和一系列脱氧形式的高度直接的全合成。进行每个合成以递送光学纯形式的靶标。对于每个合成中的关键步骤是催化不对称磷酸化反应，影响适当的desymmetrization肌醇-肌醇的前体。然后采用通用前体的面向多样性的策略对每种目标化合物进行精细加工。除三种天然产物外，还报道了几种其他简化的脱氧PI类似物的总合成方法。这些合成为这些膜相关信号分子的极性头基/生物靶标相互作用的高精度生物学研究奠定了基础。

  DOI：

  10.1021/jo060702s

文献信息

• Insights into the Structural Specificity of the Cytotoxicity of 3-Deoxyphosphatidylinositols
  作者：Yanling K. Wang、Wei Chen、Derek Blair、Mingming Pu、Yingju Xu、Scott J. Miller、Alfred G. Redfield、Thomas C. Chiles、Mary F. Roberts

  DOI：10.1021/ja710348r

  日期：2008.6.18

  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.