Octanoic acid (R)-2-[(2-cyano-ethoxy)-diisopropylamino-phosphanyloxy]-1-octanoyloxymethyl-ethyl ester | 243652-05-3

• 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: Octanoic acid (R)-2-[(2-cyano-ethoxy)-diisopropylamino-phosphanyloxy]-1-octanoyloxymethyl-ethyl ester
• 英文别名: [(2R)-3-[2-cyanoethoxy-[di(propan-2-yl)amino]phosphanyl]oxy-2-octanoyloxypropyl] octanoate
• CAS: 243652-05-3
• 化学式: C₂₈H₅₃N₂O₆P
• 分子量: 544.712
• InChiKey: DVFKGSCGTFNIBO-MFZKXUBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  37
• 可旋转键数：
  26
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  98.1
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Octanoic acid (R)-2-[(2-cyano-ethoxy)-diisopropylamino-phosphanyloxy]-1-octanoyloxymethyl-ethyl ester 在 四氮唑 、 bis(trimethylsilyl)trifluoroacetamide 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 37.0h， 生成 Octanoic acid (R)-2-{[(1R,2R,3S,4R,5R,6S)-3-(dimethoxy-phosphorylmethoxy)-4,5-bis-(dimethoxy-phosphoryloxy)-2,6-bis-methoxymethoxy-cyclohexyloxy]-hydroxy-phosphoryloxy}-1-octanoyloxymethyl-ethyl ester
  参考文献：
  名称：

  Synthesis and Biological Activity of PTEN-Resistant Analogues of Phosphatidylinositol 3,4,5-Trisphosphate

  摘要：

  The activation of phosphatidylinositol 3-kinase (PI 3-K) and subsequent production of PtdIns(3,4,5)P3 launches a signal transduction cascade that impinges on a plethora of downstream effects on cell physiology. Control of PI 3-K and PtdIns(3,4,5)P3 levels is an important therapeutic target in treatments for allergy, inflammation, cardiovascular, and malignant human diseases. We designed metabolically stabilized, that is, phosphatase resistant, analogues of PtdIns(3,4,5)P3 as probes for long-lived potential agonists or potential antagonists for cellular events mediated by PtdIns(3,4,5)P3. In particular, two types of analogues were prepared containing phosphomimetics that would be selectively resistant to the lipid 3-phosphatase PTEN. The total asymmetric synthesis of the 3-phosphorothioate-PtdIns(3,4,5)P3 and 3-methylenephosphonate-PtdIns(3,4,5)P3 analogues is described. These two analogues showed differential binding to PtdIns(3,4,5)P3 binding modules, and both were potential long-lived activators that mimicked insulin action in sodium transport in A6 cells.

  DOI：

  10.1021/ja065002j
• 作为产物：
  描述：

  辛酰氯 在 palladium on activated charcoal 吡啶 、 4-二甲氨基吡啶 、 氢气 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 20.0~55.0 ℃ 、275.79 kPa 条件下， 反应 67.0h， 生成 Octanoic acid (R)-2-[(2-cyano-ethoxy)-diisopropylamino-phosphanyloxy]-1-octanoyloxymethyl-ethyl ester
  参考文献：
  名称：

  Synthesis of short and long chain cardiolipins

  摘要：

  A phosphoramidite approach using 2-cyanoethyl N,N-diisopropylchlorophosphoramidite was utilized for the first time to synthesize short chain cardiolipins. The approach was extended to synthesize long chain and their ether analogue. Optically active 1,2-di-O-acylsn-glycerol or 1,2-di-O-myristyl-sn-glycerol was coupled with phosphoramidite reagent and 2-benzyloxy-1,3-propanediol in presence of 1H-tetrazole, followed by in situ oxidation, to give the corresponding protected cardiolipin analogues. The above intermediates were converted into cardiolipin analogues in two steps by deprotection of cyanoethyl and benzyl groups. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2006.04.071

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）。
• 5-Stabilized Phosphatidylinositol 3,4,5-Trisphosphate Analogues Bind Grp1 PH, Inhibit Phosphoinositide Phosphatases, and Block Neutrophil Migration
  作者：Honglu Zhang、Ju He、Tatiana G. Kutateladze、Takahiro Sakai、Takehiko Sasaki、Nicolas Markadieu、Christophe Erneux、Glenn D. Prestwich

  DOI：10.1002/cbic.200900545

  日期：2010.2.15

  Four ways to work: Two 5‐phosphatase resistant analogues of PtdIns(3,4,5)P3, the 5‐methylene phosphonate (MP) and 5‐phosphorothioate (PT) were synthesized and evaluated in four biochemical and biological contexts. Analogues were resistant to 5‐phosphatase activity of SHIP, bound to the PH domain of Grp1, blocked neutrophil migration, and activated sodium transport.

  四种工作方式：合成了 PTdIns(3,4,5)P 3 的两种 5-磷酸酶抗性类似物、5-亚甲基膦酸酯 (MP) 和 5-硫代磷酸酯 (PT)，并在四种生化和生物学背景下进行了评估。类似物对 SHIP 的 5-磷酸酶活性具有抗性，与 Grp1 的 PH 结构域结合，阻止中性粒细胞迁移并激活钠转运。
• Metabolically Stabilized Derivatives of Phosphatidylinositol 4-Phosphate: Synthesis and Applications
  作者：Ju He、Joanna Gajewiak、Jordan L. Scott、Denghuang Gong、Muzaffar Ali、Michael D. Best、Glenn D. Prestwich、Robert V. Stahelin、Tatiana G. Kutateladze

  DOI：10.1016/j.chembiol.2011.07.022

  日期：2011.10

  Phosphatidylinositol 4-phosphate (PtdIns(4)P) lipid is an essential component of eukaryotic membranes and a marker of the Golgi complex. Here, we developed metabolically stabilized (ms) analogs of PtdIns(4)P and the inositol 1,4-bisphosphate (IP(2)) head group derivative and demonstrated that these compounds can substitute the natural lipid fully retaining its physiological activities. The methylenephosphonate (MP) and phosphorothioate (PT) analogs of PtdIns(4)P and the aminohexyl (AH)-1P(2) probe are recognized by the PtdIns(4)P-specific PH domain of four phosphate adaptor protein 1 (FAPP1). Binding of FAPP1 to the PtdIns(4)P derivatives stimulates insertion of the PH domain into the lipid layers and induces tubulation of membranes. Both ms analogs and IP(2) probes could be invaluable for identifying protein effectors and characterizing PtdIns(4)P-dependent signaling cascades within the trans-Golgi network (TGN).
• Synthesis and biological activity of phosphatidylinositol-3,4,5-trisphosphorothioate
  作者：Honglu Zhang、Yong Xu、Nicolas Markadieu、Renaud Beauwens、Christophe Erneux、Glenn D. Prestwich

  DOI：10.1016/j.bmcl.2007.11.041

  日期：2008.1

  Metabolically-stabilized analogs of PtdIns(3,4,5)P-3 have shown long-lived agonist activity for cellular events mediated by this phosphoinositide. We describe an efficient method for the total asymmetric synthesis of the trisphosphorothioate (PT) analog of PtdIns(3,4,5)P-3- Intracellular delivery of dipalmitoyl PtdIns(3,4,5)PT3-mimicked insulin in activating sodium transport in A6 cells. (c) 2007 Elsevier Ltd. All rights reserved.