1-O-diphenylphosphate-2,4,6-tri-O-benzyl-D-myo-inositol | 376590-85-1

• 分子结构分类: 有机化合物
• 英文名称: 1-O-diphenylphosphate-2,4,6-tri-O-benzyl-D-myo-inositol
• 英文别名: (-)-2,4,6-tri-O-benzyl-myo-inositol-1-phosphate
• CAS: 376590-85-1
• 化学式: C₃₉H₃₉O₉P
• 分子量: 682.707
• InChiKey: BYMRGMPKVJMPKI-HSWMAJPMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.13
• 重原子数：
  49.0
• 可旋转键数：
  15.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  112.91
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  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 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 7.0h， 生成 2,4,6-tri-O-benzyl-5-O-tert-butyldimethylsilyl-D-myo-inositol-3-deoxy-1-diphenyl 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：

  2,4,6-Tris(benzyloxy)-1,3,5-cyclohexanetriol 、 氯磷酸二苯酯 在 Boc-His(Me)-Asn(Trt)-His(Bn)-Asn[(S)-1-MeOCO-ethyl]OtBu 三乙胺 作用下， 以 甲苯 为溶剂， 生成 1-O-diphenylphosphate-2,4,6-tri-O-benzyl-D-myo-inositol
  参考文献：
  名称：

  肌醇多磷酸盐的统一总合成：dI-3,5,6P 3，dI-3,4,5P 3，dI-3,4,6P 3和dI-3,4,5,6P 4通过催化对映选择性和定点磷酸化

  摘要：

  已经利用催化对映选择性和位点选择性磷酸化反应发现了合成各种肌醇多磷酸盐的途径。本文所述的合成方法利用一种常见的中间体来有效地获得八种独特的肌醇多磷酸酯。

  DOI：

  10.1021/jo0610816

文献信息

• Enantiodivergence in Small-Molecule Catalysis of Asymmetric Phosphorylation:  Concise Total Syntheses of the Enantiomeric <scp>d</scp>-<i>m</i><i>yo</i>-Inositol-1-phosphate and <scp>d</scp>-<i>m</i><i>yo</i>-Inositol-3-phosphate
  作者：Bianca R. Sculimbrene、Adam J. Morgan、Scott J. Miller

  DOI：10.1021/ja027402m

  日期：2002.10.1

  producing enantiomeric D-myo-inositol-1-phosphate and D-myo-inositol-3-phosphate derivatives. The catalysts were then used to complete efficient total syntheses of both D-I-1P and D-I-3P in optically pure form. Additional information is gleaned from relative rate experiments that unambiguously show the catalysts to afford enantioselection through rate accelerative pathways with respect to simple achiral

  已发现基于肽的催化剂可催化内消旋肌醇衍生的三醇 (1) 的对映发散磷酸化。随机肽库的顺序筛选，然后是重点库的评估，导致鉴定出两种肽（2 和 24），它们在产生对映体 D-myo-inositol-1-phosphate 和 D-myo-inositol 中互补-3-磷酸衍生物。然后使用催化剂完成光学纯形式的 DI-1P 和 DI-3P 的有效全合成。从相对速率实验中收集了额外的信息，这些实验明确地表明，对于简单的非手性烷基咪唑催化剂，催化剂通过速率加速途径提供对映选择。此外，溶剂效应研究表明，两种对映发散催化剂对极性介质表现出不同的耐受性。位点选择性催化剂的系统发现为未来研究区分多功能分子中独特官能团的手性催化剂奠定了基础。
• Discovery of a Catalytic Asymmetric Phosphorylation through Selection of a Minimal Kinase Mimic:  A Concise Total Synthesis of <scp>d</scp>-<i>myo</i>-Inositol-1-Phosphate
  作者：Bianca R. Sculimbrene、Scott J. Miller

  DOI：10.1021/ja016779+

  日期：2001.10.1
• 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.
• Catalyst-dependent syntheses of phosphatidylinositol-5-phosphate–DiC8 and its enantiomer
  作者：Katherine J. Kayser-Bricker、Peter A. Jordan、Scott J. Miller

  DOI：10.1016/j.tet.2008.03.037

  日期：2008.7

  Peptide-based catalysts have been applied to the enantioselective syntheses of the title Compounds, with this being the first report of the synthesis of an ent-PI5P analogue. The key steps in the synthesis involve asymmetric phosphorylation catalysis. Additional maneuvers were developed with a protecting groups scheme that enabled efficient, streamlined syntheses of these important mediators of biochemical events. (C) 2008 Elsevier Ltd. All rights reserved.
• Asymmetric Syntheses of Phosphatidylinositol-3-Phosphates with Saturated and Unsaturated Side Chains through Catalytic Asymmetric Phosphorylation
  作者：Bianca R. Sculimbrene、Yingju Xu、Scott J. Miller

  DOI：10.1021/ja0466098

  日期：2004.10.1

  Highly direct asymmetric syntheses of phosphatidylinositol-3-phosphate (PI3P) in each enantiomerically pure form have been achieved. The key step involves catalytic asymmetric phosphorylation of meso-myo-inositol derivatives through desymmetrization. Protecting group schemes have been employed that allow for synthesis of PI3P with either saturated or arachidonate side chains, in analogy to the naturally occurring systems. Syntheses in each enantiomeric series are reported that rely on the choice of enantioselective peptide-based catalyst to define the enantiomeric series in which the syntheses are carried out.