3,4,5,6-tetra-O-benzyl-1-O-p-methoxybenzyl-D-myo-inositol | 170900-81-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3,4,5,6-tetra-O-benzyl-1-O-p-methoxybenzyl-D-myo-inositol
• 英文别名: 3,4,5,6-tetra-O-benzyl-1-O-(4-methoxybenzyl)-myo-inositol；(1R,2R,3S,4S,5R,6S)-2-[(4-methoxyphenyl)methoxy]-3,4,5,6-tetrakis(phenylmethoxy)cyclohexan-1-ol
• CAS: 170900-81-9
• 化学式: C₄₂H₄₄O₇
• 分子量: 660.807
• InChiKey: VRHOTTZVJLLNQT-WRRHOSNLSA-N

物化性质

• 沸点：
  756.5±60.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  49
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  75.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3,4,5,6-tetra-O-benzyl-1-O-p-methoxybenzyl-D-myo-inositol 在 咪唑 、 碘 、 三苯基膦 作用下， 以 甲苯 为溶剂， 反应 41.0h， 以68%的产率得到D-1,4,5,6-tetra-O-benzyl-2-deoxy-2-iodo-3-O-(4-methoxybenzyl)-scyllo-inositol
  参考文献：
  名称：

  2-Deoxy Derivative Is a Partial Agonist of the Intracellular Messenger Inositol 3,4,5,6-Tetrakisphosphate in the Epithelial Cell Line T₈₄

  摘要：

  We have synthesized the first deoxy analogues of myo-inositol 3,4,5,6-tetrakisphosphate (1) [Ins(3,4,5,6)P-4], rac-2-deoxy-myo-inositol 3,4,5,6-tetrakisphosphate (rac-2), 2-deoxy-myo-inositol 1,4,5,6-tetrakisphosphate (ent-2), and rac-1-deoxy-myo-inositol 3,4,5,6-tetrakisphosphate (rac-3). In order to evaluate the binding properties of the three derivatives to the yet unidentified intracellular binding sites for Ins(3,4,5,6)P4, the analogues were converted to membrane-permeant derivatives. Starting with common inositol precursors, various forms of Barton-McCombie deoxygenation and classical protection/deprotection procedures yielded the desired precursors rac-1-O-butyryl-2-deoxy-myo-inositol (rac-12), ent-3-O-butyryl-2-deoxy-myo-inositol (ent-12), and rac-2-O-butyryl-1-deoxy-myo-inositol (rac-19), respectively. Phosphorylation and subsequent deprotection yielded rac-2, ent-2, and rac-3. Alternatively, phosphorylation followed by alkylation with acetoxymethyl bromide gave the membrane-permeant derivatives 1-O-butyryl-2-deoxy-myo-inositol 3,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester (rac-5), 3-O-butyryl-2-deoxy-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester (ent-5), and 2-O-butyryl-1-deoxy-myo-inositol 3,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester (rac-6), respectively. We examined the potency of the membrane-permeant deoxy derivatives in inhibition of calcium-mediated chloride secretion (CaMCS) in intact T-84 cells. Compared to the 1,2-di-O-butyryl-myo-inositol 3,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester (4), the membrane-permeant derivative of Ins(3,4,5,6)P-4 (1), the 2-deoxy derivative (rac-5) exhibited a slightly weaker inhibitory effect, while the enantiomerically pure 2-deoxy-Ins(1,4,5,6)P-4 (ent-5) and the l-deoxy derivative (rac-6) were inactive. As expected, the effect was stereoselective. Thus, the l-hydroxyl group is apparently essential for binding and the inhibitory effect of Ins(3,4,5,6)P4 on chloride secretion, whereas the 2-hydroxyl group plays a less important role.

  DOI：

  10.1021/jm970781n
• 作为产物：
  描述：

  溴甲苯 在 sodium hydride 、 二正丁基氧化锡 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 7.5h， 生成 3,4,5,6-tetra-O-benzyl-1-O-p-methoxybenzyl-D-myo-inositol
  参考文献：
  名称：

  白念珠菌的磷脂质甘露聚糖的全合成。

  摘要：

  首先，在细胞表面phospholipomannan锚[β-曼的总合成p - （1→2）-β-曼p ] ñ - （1→2）-β-曼p - （1→2）-α-曼p -1→ P - （ø →6）-α-曼p - （1→2）肌醇-1- P - （ø →1）的-phytoceramide白色念珠菌被报道。目标磷酸脂甘露聚糖（PLM）锚提出了合成难题，例如异常的动力学控制（1→2）-β-寡甘露聚糖结构域，异头磷酸二酯和独特的通过磷酸基团与聚糖连接的植物神经酰胺脂质尾巴。PLM锚的合成是通过收敛嵌段合成方法完成的，该方法使用了三个主要的受到适当保护的结构单元：（1→2）-β-四甘露聚糖重复序列，假二糖和植物神经酰胺-1- H-膦酸酯。使用预激活方法在一锅中合成最具挑战性的（1→2）-β-四甘露聚糖域。通过对映选择性A 3三组分偶联反应合成了植物神经酰胺-1- H-膦酸酯。最后，植物神经酰胺-1- H膦酸二部

  DOI：

  10.1021/acs.joc.0c00402

文献信息

• SYNTHETIC ANALOGUES OF PHOSPHATIDYL-MYO-INOSITOL MANNOSIDES WITH AN INHIBITORY ACTIVITY OF THE INFLAMMATORY RESPONSE
  申请人：Quesniaux Fyffel Valérie

  公开号：US20110224162A1

  公开（公告）日：2011-09-15

  The present invention relates to novel synthetic analogues of phosphatidyl-myo-inositol mannosides (hereinafter referred to as PIMs) of general formula (I): or a pharmaceutically acceptable salt thereof, to the method for preparing same and to the use thereof in the prevention or treatment of a disease associated with the overexpression of cytokines or of chemokines, in particular of TNF and/or of IL-12. The invention also relates to a pharmaceutical composition comprising at least one synthetic derivative of PIM.

  本发明涉及磷脂酰肌醇甘露聚糖的新型合成类似物（以下简称为PIMs），其一般公式为（I）或其药学上可接受的盐，以及其制备方法和在预防或治疗与细胞因子或趋化因子过表达相关的疾病中的应用，特别是TNF和/或IL-12。该发明还涉及包含至少一种PIM的合成衍生物的药物组合物。
• Synthesis and Kinetic Evaluation of Inhibitors of the Phosphatidylinositol-Specific Phospholipase C from <i>Bacillus cereus</i>
  作者：Stephen F. Martin、Allan S. Wagman

  DOI：10.1021/jo960850q

  日期：1996.11.15

  Substrate analogues of phosphatidylinositol (1) were synthesized and evaluated as potential inhibitors of the bacterial phosphatidylinositol-specific phospholipase C (PI-PLC) from Bacillus cereus. The chiral analogues of the water-soluble phospholipid substrate 5 were designed to probe the effects of varying the inositol C-2 hydroxyl group, which is generally believed to serve as the nucleophile in

  合成了磷脂酰肌醇（1）的底物类似物，并评估为蜡状芽孢杆菌的细菌磷脂酰肌醇特异性磷脂酶C（PI-PLC）的潜在抑制剂。水溶性磷脂底物5的手性类似物被设计成探测改变肌醇C-2羟基的作用，通常认为它通过PI-PLC在磷脂酰肌醇水解的第一步中用作亲核试剂。在类似物6-9中，磷脂酰肌醇衍生物的肌醇环上的C-2羟基以几种方式被合理地改变。肌醇环C-2处的立体化学颠倒导致了scyllo衍生物6。肌醇C-2羟基被氟取代，以产生烷基-氟代肌醇7，氢原子被取代以提供2-脱氧化合物8。C-2羟基被O-甲基化以制备甲氧基衍生物9. C-2处的天然肌醇构型保留在不可水解的二硫代磷酸酯类似物10中。然后使用D-肌醇1-（4-硝基苯基）在连续测定法中分析这些类似物对PI-PLC的抑制作用（25）作为发色底物。确定了每种磷脂酰肌醇衍生物的动力学参数，发现它们是具有K（i）的竞争性抑制剂，如下：6,0.2mM; 10，0.6毫米;
• The synthesis of 1-O-(2-N-stearoyl-D-erythro-sphinganinel-phosphoryl)-2-O-(α-D-mannopyranosyl-D-myo-inositol: a fragment of the naturally occurring inositol-containing glycophosphosphingolipids
  作者：Alla Yu. Zamyatina、Vitahy I. Shvets

  DOI：10.1016/0009-3084(95)02446-p

  日期：1995.6

  sphingophospholipid was synthesized from D-erythro ceramide and optically active mannosyl-myo-inositol with the use of phosphite triester coupling procedure. The optical resolution of racemic 3,4,5,6-tetra-O-benzyl-myo-inositol to enantiomers was accomplished via diastereomeric menthoxyacetic esters. Iodonium ion-promoted glycosylation has been used for the preparation of chiral mannosyl-myo-inositol. Bis(diisoprop

  利用亚磷酸酯三酯偶联法，由D-赤型神经酰胺和旋光性甘露糖基-肌醇合成了含有鞘磷脂的手性甘露糖基肌醇。外消旋的3,4,5,6-四-O-苄基-肌肌醇对映体的旋光拆分是通过非对映体薄荷醇乙酸酯实现的。碘鎓离子促进的糖基化已用于制备手性甘露糖基-肌醇。双（二异丙基氨基）-2-氰基乙基膦已被用于引入D-赤型-3-O-苯甲酰基神经酰胺的伯羟基官能团与旋光和部分苄基的1-O-（2的仲羟基之间的磷酸二酯键-O-α-D-甘露吡喃糖基）-D-肌醇
• Nonhydrolyzable analogs of phosphatidylinositol as ligands of phospholipases C
  作者：Cornelia Mihai、Xiangjun Yue、Li Zhao、Alex Kravchuk、Ming-Daw Tsai、Karol S. Bruzik

  DOI：10.1039/b9nj00629j

  日期：——

  Phosphatidylinositol-specific phospholipases C (PI-PLCs) are important enzymes participating in transmembrane signal transduction. The structures of the two major species of these enzymes: bacterial Ca2+-nondependent enzyme from B. cereus and mammalian Ca2+-dependent PLCδ1 from rat brain in the complexes with the polar head groups of their substrates have been previously solved. Although these structures show few differences as compared to free enzymes, there is a compelling evidence that full catalytic activity of PI-PLC necessitates interaction of the enzyme with the entire substrate, including the hydrophobic fatty acid chains. In this work we develop new tightly binding and cleavage-resistant analogs of phosphatidylinositol, using relatively minor modifications of the structure. Two synthesized analogs, 2-amino-2-deoxy-PI (8) and the conformationally constrained analog (10) had binding affinities (Ki) in 10 μM range. 15N-1H HSQC NMR spectra of uniformly 15N-labeled bacterial Ca2+-nondependent and Ca2+-dependent phospholipases C, btPLC and saPLC1, respectively, displayed changes upon ligand binding that suggest an occurrence of a conformational change.

  磷脂酰肌醇特异性磷脂酶 C（PI-PLCs）是参与跨膜信号转导的重要酶。这些酶的两个主要种类：来自 B. cereus 的不依赖 Ca2+ 的细菌酶和来自大鼠大脑的依赖 Ca2+ 的哺乳动物 PLCδ1 与其底物极性头基的复合物的结构以前已经解决。虽然这些结构与游离酶相比几乎没有什么不同，但有令人信服的证据表明，PI-PLC 的全部催化活性需要酶与整个底物（包括疏水性脂肪酸链）的相互作用。在这项工作中，我们对磷脂酰肌醇的结构进行了相对较小的修改，开发出了新的紧密结合且抗裂解的类似物。合成的两种类似物--2-氨基-2-脱氧-PI（8）和构象约束类似物（10）的结合亲和力（Ki）在 10 μM 范围内。15N-1H HSQC NMR 光谱显示，15N 标记的细菌 Ca2+ 非依赖性磷脂酶 C 和 Ca2+ 依赖性磷脂酶 C（btPLC 和 saPLC1）在与配体结合后发生了变化，表明发生了构象变化。
• Introducing Oxo-Phenylacetyl (OPAc) as a Protecting Group for Carbohydrates
  作者：Atul Kumar、Veeranjaneyulu Gannedi、Suhail A. Rather、Ram A. Vishwakarma、Qazi Naveed Ahmed

  DOI：10.1021/acs.joc.9b00126

  日期：2019.4.5

  A series of oxo-phenylacetyl (OPAc)-protected saccharides, with divergent base sensitivity profiles against benzoyl (Bz) and acetyl (Ac) were synthesized, and KHSO5/AcCl in methanol was identified as an easy, mild, selective, and efficient deprotecting reagent for their removal in the perspective of carbohydrate synthesis. Timely monitoring of AcCl reagent was supportive in both sequential and simultaneous

  合成了一系列对苯甲酰基（Bz）和乙酰基（Ac）具有不同敏感性的羰基-苯基乙酰基（OPAc）保护的糖，并确定了甲醇中KHSO 5 / AcCl是一种容易，温和，选择性和高效的化合物从碳水化合物合成的角度来看，脱保护剂可将其去除。及时监测AcCl试剂有助于OPAc，Bz和Ac的顺序和同时脱保护。我们方法的显着特征是针对不同基团的正交稳定性，使用设计的单糖易于生成不同有价值的受体，以及使用OPAc作为糖基供体。