(+)-2,4,6-tri-O-benzyl-myo-inositol-3-phosphate | 474404-92-7

• 分子结构分类: 有机化合物
• 英文名称: (+)-2,4,6-tri-O-benzyl-myo-inositol-3-phosphate
• CAS: 474404-92-7
• 化学式: C₃₉H₃₉O₉P
• 分子量: 682.707
• InChiKey: BYMRGMPKVJMPKI-MVZBGDKDSA-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：

  (+)-2,4,6-tri-O-benzyl-myo-inositol-3-phosphate 在 咪唑 、 四氮唑 、 sodium hydride 、 氟化氢吡啶 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 86.0h， 生成 Octanoic acid (R)-2-{benzyloxy-[(1S,2S,3R,4S,5R,6R)-2,4,6-tris-benzyloxy-3-(bis-benzyloxy-phosphoryloxy)-5-hydroxy-cyclohexyloxy]-phosphanyloxy}-1-octanoyloxymethyl-ethyl ester
  参考文献：
  名称：

  Asymmetric Syntheses of Phosphatidylinositol-3-Phosphates with Saturated and Unsaturated Side Chains through Catalytic Asymmetric Phosphorylation

  摘要：

  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.

  DOI：

  10.1021/ja0466098
• 作为产物：
  描述：

  2,4,6-Tris(benzyloxy)-1,3,5-cyclohexanetriol 、 氯磷酸二苯酯 在 Boc-ϖ(Me)-t-BuHyp-spiro-5-Tyr(O-t-Bu)-Phe-OMe 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 4.0h， 以56%的产率得到(+)-2,4,6-tri-O-benzyl-myo-inositol-3-phosphate
  参考文献：
  名称：

  不对称磷酸化小分子催化中的对映发散：对映体-肌醇-1-磷酸和d-肌-肌醇-3-磷酸的简明全合成

  摘要：

  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。

  DOI：

  10.1021/ja027402m

文献信息

• New Reagents for the Synthesis of Arylmethyl Ethers and Esters
  作者：Gregory Dudley、Philip Albiniak

  DOI：10.1055/s-0029-1219531

  日期：2010.4

  developmentof new arylmethyl transfer (benzylation) reagents for protectingoxygen functional groups under relatively mild and neutral conditions.It begins with an investigation of organosiletanes as surrogatehydroxyl groups, which inspired siletane-functionalized benzyl ethersand forced us to confront the difficulties associated with the synthesisof benzyl ethers. The end result is a new series of neutral oxypyridiniumsalts

  该帐户记录了导致开发新的芳甲基转移（苄基化）试剂在相对温和和中性条件下保护氧官能团的努力。它从作为替代羟基的有机硅酮的研究开始，它启发了硅烷官能化的苄基醚并迫使我们面对与苄基醚合成相关的困难。最终结果是一系列新的中性氧吡啶鎓盐，用于在温和条件下对各种亲核官能团进行苄基化。1 引言 2 应变有机硅烷的 Tamao 型氧化 3 P-Siletanylbenzyl (PSB) 保护基团 4 2-Benzyloxy-1-methylpyridinium Triflate 5 Friedel-Crafts 反应和机理洞察 6 苄酯形成 7 取代的 Benz8 转移试剂和展望
• Unified Total Syntheses of the Inositol Polyphosphates:  <scp>d</scp>-I-3,5,6P₃, <scp>d</scp>-I-3,4,5P₃, <scp>d</scp>-I-3,4,6P₃, and <scp>d</scp>-I-3,4,5,6P₄ via Catalytic Enantioselective and Site-Selective Phosphorylation
  作者：Adam J. Morgan、Shio Komiya、Yingju Xu、Scott J. Miller

  DOI：10.1021/jo0610816

  日期：2006.9.1

  Synthetic routes to various inositol polyphosphates have been discovered utilizing catalytic enantioselective and site-selective phosphorylation reactions. The syntheses described herein exploit a common intermediate to gain efficient access to eight unique inositol polyphosphates.

  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。
• Streamlined Synthesis of Phosphatidylinositol (PI), PI3P, PI3,5P₂, and Deoxygenated Analogues as Potential Biological Probes
  作者：Yingju Xu、Bianca R. Sculimbrene、Scott J. Miller

  DOI：10.1021/jo060702s

  日期：2006.6.1

  Highly direct total syntheses of phosphatidylinositol (PI), phosphatidylinositol-3-phosphate (PI3P), phosphatidylinositol-3,5-bisphosphate (PI3,5P2), and a range of deoxygenated versions are reported. Each synthesis is carried out to deliver the target in optically pure form. The key step for each synthesis is a catalytic asymmetric phosphorylation reaction that affects desymmetrization of an appropriate

  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。
• Asymmetric Syntheses of l,l<i>-</i>and l,d<i>-</i>Di-<i>myo</i>-inositol-1,1′-phosphate and their Behavior as Stabilizers of Enzyme Activity at Extreme Temperatures
  作者：Christina M. Longo、Yang Wei、Mary F. Roberts、Scott J. Miller

  DOI：10.1002/anie.200900480

  日期：2009.5.25

  The big “DIP”per: The preparation of both l,l‐DIP and l,d‐DIP (see structures) involves a complex case of double asymmetric induction in the key step of the synthesis. The differential ability of each isomer to contribute to thermoprotection in the context of a key enzyme has been assessed and both isomers of DIP are shown to possess biological activity.

  大“DIP”per：l,l -DIP 和l,d -DIP（见结构）的制备在合成的关键步骤中涉及双重不对称诱导的复杂情况。已经评估了每种异构体在关键酶的背景下有助​​于热保护的不同能力，并且 DIP 的两种异构体都显示出具有生物活性。
• 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.