α-D-glucose-1-phosphate tributylammonium salt | 61503-56-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: α-D-glucose-1-phosphate tributylammonium salt
• CAS: 61503-56-8
• 化学式: C₆H₁₃O₉P*C₁₂H₂₇N
• 分子量: 445.491
• InChiKey: QRAKZZNBMIVWOQ-RRNUZJGBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.58
• 重原子数：
  29.0
• 可旋转键数：
  12.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  160.15
• 氢给体数：
  6.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  uridine 5'-diphosphate, tributylammonium 、 α-D-glucose-1-phosphate tributylammonium salt 在 N,N'-二异丙基碳二亚胺 、 magnesium chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 Up3-[1]glucose
  参考文献：
  名称：

  Pyrimidine Ribonucleotides with Enhanced Selectivity as P2Y₆ Receptor Agonists: Novel 4-Alkyloxyimino, (S)-Methanocarba, and 5′-Triphosphate γ-Ester Modifications

  摘要：

  The P2Y(6) receptor is a cytoprotective G-protein-coupled receptor (GPCR) activated by UDP (EC50 = 0.30 mu M). We compared and combined modifications to enhance P2Y(6) receptor agonist selectivity, including ribose ring constraint, 5-iodo and 4-alkyloxyimino modifications, and phosphate modifications such as alpha,beta-methylene and extension of the terminal phosphate group into gamma-esters of UTP analogues. The conformationally constrained (S)-methanocarba-UDP is a full agonist (EC50 = 0.042 mu M). 4-Methoxyimino modification of pyrimidine enhanced P2Y(6), preserved P2Y(2) and P2Y(4), and abolished P2Y(14) receptor potency, in the appropriate nucleotide. N-4-Benzyloxy-CDP (15, MRS2964) and N-4-methoxy-Cp3U Cp3U (12, MRS2957) were potent, selective P2Y(6) receptor agonists (EC50 of 0.026 and 0.012 mu M, respectively). A hydrophobic binding region near the nucleobase was explored with receptor modeling and docking. UTP-gamma-aryl and cycloalkyl phosphoesters displayed only intermediate P2Y(6) receptor potency but had enhanced stability in acid and cell membranes. UTP-glucose was inactive, but its (S)-methanocarba analogue and N-4-methoxycytidine 5'-triphospho-gamma-[1]glucose were active (EC50 of 2.47 and 0.18 mu M, respectively). Thus, the potency, selectivity, and stability of pyrimidine nucleotides as P2Y(6) receptor agonists may be enhanced by modest structural changes.

  DOI：

  10.1021/jm100287t
• 作为产物：
  描述：

  三正丁胺 、 α-D-glucose 1-phosphate disodium salt 在 ion exchange resin (DOWEX 50WX₂-200 (H)) 作用下， 生成 α-D-glucose-1-phosphate tributylammonium salt
  参考文献：
  名称：

  Pyrimidine Nucleotides with 4-Alkyloxyimino and Terminal Tetraphosphate δ-Ester Modifications as Selective Agonists of the P2Y₄ Receptor

  摘要：

  P2Y(2) and P2Y(4) receptors are G protein-coupled receptors, activated by UTP and dinudeoside tetraphosphates, which are difficult to distinguish pharmacologically for lack of potent and selective ligands. We structurally varied phosphate and uracil moieties in analogues of pyrimidine nucleoside 5'-triphosphates and 5'-tetraphosphate esters. P2Y(4) receptor potency in phospholipase C stimulation in transfected 1321N1 human astrocytoma cells was enhanced in N-4-alkyloxycytidine derivatives. OH groups on a terminal delta-glucose phosphoester of uridine 5'-tetraphosphate were inverted or substituted with H or F to probe H-bonding effects. N-4-(Phenylpropoxy)-CTP 16 (MRS4062), Up(4)-[1]3'-deoxy-3'-fluoroglucose 34 (MRS2927), and N-4-(phenylethoxy)-CTP 15 exhibit >= 10-fold selectivity for human P2Y(4) over P2Y(2) and P2Y(6) receptors (EC50 values 23, 62, and 73 nM, respectively). delta-3-Chlorophenyl phosphoester 21 of Up(4) activated P2Y(2) but not P2Y(4) receptor. Selected nucleotides tested for chemical and enzymatic stability were much more stable than UTP. Agonist docking at CXCR4-based P2Y(2) and P2Y(4) receptor models indicated greater steric tolerance of N-4-phenylpropoxy group at P2Y(4). Thus, distal structural changes modulate potency, selectivity, and stability of extended uridine tetraphosphate derivatives, and we report the first P2Y(4) receptor-selective agonists.

  DOI：

  10.1021/jm101591j

文献信息

• Molecular recognition in the P2Y14 receptor: Probing the structurally permissive terminal sugar moiety of uridine-5′-diphosphoglucose
  作者：Hyojin Ko、Arijit Das、Rhonda L. Carter、Ingrid P. Fricks、Yixing Zhou、Andrei A. Ivanov、Artem Melman、Bhalchandra V. Joshi、Pavol Kováč、Jan Hajduch、Kenneth L. Kirk、T. Kendall Harden、Kenneth A. Jacobson

  DOI：10.1016/j.bmc.2009.05.024

  日期：2009.7

  substitution by chain extension through an amide linkage. Functionalized congeners containing terminal 2-acylaminoethylamides prepared by this strategy retained P2Y14 activity, and molecular modeling predicted close proximity of this chain to the second extracellular loop of the receptor. In addition, replacement of glucose with other sugars did not diminish P2Y14 potency. For example, the [5′′]ribose derivative

  P2Y 14受体是一种核苷酸信号蛋白，由尿苷-5'-二磷酸葡萄糖1和其他尿嘧啶核苷酸激活。我们已经确定1的葡萄糖部分是设计该 P2Y 14激动剂类似物的最结构允许区域。例如，尿苷-5'-二磷酸葡萄糖醛酸的羧酸酯基团被证明适用于通过酰胺键进行链延伸的灵活取代。通过该策略制备的含有末端 2-酰基氨基乙基酰胺的功能化同源物保留了 P2Y 14活性，分子模型预测该链与受体的第二个细胞外环非常接近。此外，用其他糖替代葡萄糖不会降低 P2Y 14效力。例如，[5'']核糖衍生物的EC 50为0.24 μM。的葡萄糖部分的选择性monofluorination指示用于2'角色' -和6'' -的羟基1受体识别。β-葡萄糖苷的效力比天然 α-异构体低两倍，但 1''-氧的亚甲基替代消除了活性。用环戊基或刚性双环 [3.1.0] 己烷基团取代核糖环系统消除了活性。Uridine-5'-diphosphoglucose
• Stereospecific synthesis of sugar-1-phosphates and their conversion to sugar nucleotides
  作者：Shannon C. Timmons、David L. Jakeman

  DOI：10.1016/j.carres.2008.01.046

  日期：2008.4

  products, efficient access to stereopure sugar nucleotide donor substrates is required. Herein, the rapid synthesis and purification of eight sugar nucleotides is described by a facile 30 min activation of nucleoside 5'-monophosphates bearing purine and pyrimidine bases with trifluoroacetic anhydride and N-methylimidazole, followed by a 2 h coupling with stereospecifically prepared sugar-1-phosphates. Tributylammonium

  随着Leloir糖基转移酶越来越多地用于制备寡糖，糖结合物和糖基化天然产物，需要有效地获得立体纯糖核苷酸供体底物。本文中，通过用三氟乙酸酐和N-甲基咪唑将带有嘌呤和嘧啶碱基的核苷5'-单磷酸核苷轻松活化30分钟，然后与立体定向制备的糖-1偶联2小时，从而快速合成和纯化八个糖核苷酸-磷酸盐。碳酸氢三丁铵和乙酸三丁铵是分别用于6-脱氧糖核苷酸和己糖或戊糖衍生糖核苷酸的C18反相纯化的离子对试剂。