1,2-Di-O-octanoyl-sn-glycerol benzyl (N,N-diisopropylamino)phosphoramidite | 163563-71-1

• 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: 1,2-Di-O-octanoyl-sn-glycerol benzyl (N,N-diisopropylamino)phosphoramidite
• 英文别名: (2R)-3-(((benzyloxy)(diisopropylamino)phosphaneyl)oxy)propane-1,2-diyl dioctanoate；1,2-di-O-octanoyl-sn-glycerol 3-(benzyl N,N-diisopropyl)phosphoramidite；[(2R)-3-[[di(propan-2-yl)amino]-phenylmethoxyphosphanyl]oxy-2-octanoyloxypropyl] octanoate
• CAS: 163563-71-1
• 化学式: C₃₂H₅₆NO₆P
• 分子量: 581.773
• InChiKey: STGHOXTZWOBOTM-OKVUXXRHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.2
• 重原子数：
  40
• 可旋转键数：
  26
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  74.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1,2-Di-O-octanoyl-sn-glycerol benzyl (N,N-diisopropylamino)phosphoramidite 在 palladium on activated charcoal 四氮唑 、 氢气 、 双氧水 、 碳酸氢钠 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 18.0h， 生成
  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：

  1,2-十八酰基-sn-甘油 、 苄基N,N,N',N'-四异丙基亚磷酰二胺 在 四氮唑 作用下， 以 二氯甲烷 为溶剂， 以71%的产率得到1,2-Di-O-octanoyl-sn-glycerol benzyl (N,N-diisopropylamino)phosphoramidite
  参考文献：
  名称：

  A synthesis of dioctanoyl phosphatidylinositol

  摘要：

  A synthesis of the naturally occurring enantiomer of phosphatidylinositol is reported. A resolution strategy, using camphor as a chiral auxiliary is employed to obtain the desired, enantiomerically pure, inositol derivative. Dioctanoyl lipid chains are appended to the molecule, which are shorter than the naturally occurring lipid chains, providing the molecule with enhanced water solubility. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2009.11.026

文献信息

• Design and synthesis of the penta(acetoxymethyl) ester of dioctanoyl phosphatidylinositol-3,5-bisphosphate
  作者：Naoki Kanoh、Kosuke Mano、Daisuke Saigusa、Takeo Usui、Yoshiharu Iwabuchi

  DOI：10.1016/j.bmcl.2016.10.046

  日期：2016.12

  membrane-permeant analogs of phosphatidylinositol phosphates (PIPs) is a useful strategy for understanding the cellular roles of PIPs as well as the mode of action of drugs whose biological activity is associated with PIPs. We herein established the synthetic route to the dioctanoyl analogue of phosphatidylinositol 3,5-bisphosphate (di-C8-PI(3,5)P2) and its penta(acetoxymethyl) ester (di-C8-PI(3,5)P2/5AM)

  胞外施用磷脂酰肌醇磷酸酯（PIP）的水溶性和膜渗透性类似物是了解PIP的细胞作用以及其生物学活性与PIP相关的药物作用方式的有用策略。我们在此建立了磷脂酰肌醇3,5-双磷酸酯（di-C 8 -PI（3,5）P 2）及其五（乙酰氧基甲基）酯（di-C 8 -PI（3,5 ）的二辛酰基类似物的合成路线P 2 / 5AM）。
• Synthesis and biological evaluation of phosphatidylinositol phosphate affinity probes
  作者：Stuart J. Conway、James Gardiner、Simon J. A. Grove、Melloney K. Johns、Ze-Yi Lim、Gavin F. Painter、Diane E. J. E. Robinson、Christine Schieber、Jan W. Thuring、Leon S.-M. Wong、Meng-Xin Yin、Antony W. Burgess、Bruno Catimel、Phillip T. Hawkins、Nicholas T. Ktistakis、Leonard R. Stephens、Andrew B. Holmes

  DOI：10.1039/b913399b

  日期：——

  The synthesis of the complete family of phosphatidylinositol phosphate analogues (PIPs) from five key core intermediates A–E is described. These core compounds were obtained from myo-inositol orthoformate 1via regioselective DIBAL-H and trimethylaluminium-mediated cleavages and a resolution–protection process using camphor acetals 10. Coupling of cores A–E with phosphoramidites 34 and 38, derived from the requisite protected lipid side chains, afforded the fully-protected PIPs. Removal of the remaining protecting groups was achieved via hydrogenolysis using palladium black or palladium hydroxide on carbon in the presence of sodium bicarbonate to afford the complete family of dipalmitoyl- and amino-PIP analogues 42, 45, 50, 51, 58, 59, 67, 68, 76, 77, 82, 83, 92, 93, 99 and 100. Investigations using affinity probes incorporating these compounds have identified novel proteins involved in the PI3K intracellular signalling network and have allowed a comprehensive proteomic analysis of phosphoinositide interacting proteins.

  报道了从五个关键的核心中间体A-E合成完整的磷脂酰肌醇磷酸类似物（PIPs）家族的方法。这些核心化合物通过选择性DIBAL-H和三甲基铝介导的裂解以及使用樟脑乙缩醛的解析保护过程，从肌醇原甲酸1中获得。将核心A-E与从所需保护的脂质侧链衍生的磷酰胺34和38偶联，得到了完全保护的PIPs。通过使用钯黑或碳上的钯氢氧化物在碳酸氢钠存在下的氢解，去除了剩余的保护基团，得到了完整的二棕榈酰和氨基PIP类似物42、45、50、51、58、59、67、68、76、77、82、83、92、93、99和100。利用包含这些化合物的亲和探针进行的研究，鉴定了参与PI3K细胞内信号网络的新蛋白，并允许对磷脂酰肌醇相互作用蛋白进行全面的蛋白质组学分析。
• 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。
• Membrane-Permeant 3-OH-Phosphorylated Phosphoinositide Derivatives
  作者：Carlo Dinkel、Mark Moody、Alexis Traynor-Kaplan、Carsten Schultz

  DOI：10.1002/1521-3773(20010817)40:16<3004::aid-anie3004>3.0.co;2-o

  日期：2001.8.17

  A crucial role in the regulation of epithelial chloride secretion is played by the phosphoinositide PtdIns(3,4,5)P3 . Membrane-permeant derivatives of this and other naturally occurring phosphoinositides have been synthesized. These derivatives, which can be bioactivated, were used in investigations on nasal epithelia of patients suffering from cystic fibrosis.
• Membrane-Permeant Phosphoinositide Derivatives as Modulators of Growth Factor Signaling and Neurite Outgrowth
  作者：Vibor Laketa、Sirus Zarbakhsh、Eva Morbier、Devaraj Subramanian、Carlo Dinkel、Justin Brumbaugh、Pascale Zimmermann、Rainer Pepperkok、Carsten Schultz

  DOI：10.1016/j.chembiol.2009.10.005

  日期：2009.11

  Phosphoinositides are important signaling molecules that govern a large number of cellular processes such as proliferation, differentiation, membrane remodeling, and survival. Here we introduce a fully synthetic membrane-permeant derivative of a novel, easily accessible, and very potent phosphatidylinositol 3,4,5-trisphosphate [Ptdlns(3,4,5)P-3] mimic: phosphatidylinositol 3,4,5,6-tetrakisphosphate [Ptdlns(3,4,5,6)P-4]. The membrane-permeant PtdIns(3,4,5,6)P-4 derivative activated pathways downstream of phosphatidylinositol 3-kinase (PI3K), including protein kinase 13, p70S6K, mitogen-activated protein kinase, and protein kinase C, more potently than similar membrane-permeant PtdIns(3,4,5)P-3 and PtdIns(3,4)P-2 derivatives in the absence of receptor stimulation. In addition, we demonstrate that treatment of PC12 cells with the membrane-permeant PtdIns(3,4)P-2, PtdIns(3,4,5)P-3, and Ptdlns(3,4,5,6)P-4 derivatives increases the number of neurites per cell in the presence of NGF. This work establishes membrane-permeant phosphoinositides as powerful tools to study PI3K signaling and directly demonstrates that 3-phosphorylated phosphoinositides are instrumental for neurite initiation.