异鼠李亭 3-O-beta-葡糖苷酸 | 36687-76-0

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 中文名称: 异鼠李亭 3-O-beta-葡糖苷酸
• 中文别名: 异鼠李素-3-葡萄糖醛酸苷；异鼠李亭3-O-beta-葡糖苷酸
• 英文名称: Isorhamnetin 3-glucuronide
• 英文别名: 3-O-β-D-glucopyranuronosyl-3'-O-methylquercetin；isorhamnetin 3-O-β-D-glucuronopyranoside；isorhamnetin-3-O-β-D-glucuronopyranoside；isorhamnetin 3-O-β-glucuronopyranoside；isorhamnetin 3-O-β-D-glucuronide；isorhamnetin-3-O-β-D-glucuronide；(2S,3S,4S,5R,6S)-6-[5,7-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-4-oxochromen-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid
• CAS: 36687-76-0
• 化学式: C₂₂H₂₀O₁₃
• 分子量: 492.393
• InChiKey: VVZWHOMBDMMRSC-NTKSAMNMSA-N

物化性质

• 沸点：
  884.9±65.0 °C(Predicted)
• 密度：
  1.83±0.1 g/cm3(Predicted)
• 溶解度：
  溶于氯仿、二氯甲烷、乙酸乙酯、DMSO、丙酮等。

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  213
• 氢给体数：
  7
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  乙酰溴-Alpha-D-葡萄糖酮酸甲基酯 在 palladium dihydroxide 、 溶剂黄146 吡啶 、 calcium sulfate 、 sodium carbonate 、 silver(l) oxide 、 环己烯 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 3.0h， 生成 异鼠李亭 3-O-beta-葡糖苷酸
  参考文献：
  名称：

  Convenient syntheses of metabolically important quercetin glucuronides and sulfates

  摘要：

  Synthetic approaches to the major human plasma metabolites of quercetin, quercetin 3'-sulfate and the beta-D-glucopyranosiduronic acid derivatives 3'-methylquercetin 3-glucuronide (isorhamnetin 3-glucuronide), quercetin 3-glucuronide and quercetin 3'-glucuronide are described. This is the first report of the chemical synthesis of quercetin 3'-glucuronide. All procedures start from the same precursor, 4',7-di-O-benzylquercetin, and all are more convenient than existing methods. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2006.04.102

文献信息

• Three-Dimensional Quantitative Structure-Activity Relationship Studies on UGT1A9-Mediated 3-O-Glucuronidation of Natural Flavonols Using a Pharmacophore-Based Comparative Molecular Field Analysis Model
  作者：Baojian Wu、John Kenneth Morrow、Rashim Singh、Shuxing Zhang、Ming Hu

  DOI：10.1124/jpet.110.175356

  日期：2011.2

  Glucuronidation is often recognized as one of the rate-determining factors that limit the bioavailability of flavonols. Hence, design and synthesis of more bioavailable flavonols would benefit from the establishment of predictive models of glucuronidation using kinetic parameters [e.g., K m, V max, intrinsic clearance (CLint) = V max/ K m] derived for flavonols. This article aims to construct position (3-OH)-specific comparative molecular field analysis (CoMFA) models to describe UDP-glucuronosyltransferase (UGT) 1A9-mediated glucuronidation of flavonols, which can be used to design poor UGT1A9 substrates. The kinetics of recombinant UGT1A9-mediated 3-O-glucuronidation of 30 flavonols was characterized, and kinetic parameters ( K m, V max, CLint) were obtained. The observed K m, V max, and CLint values of 3-O-glucuronidation ranged from 0.04 to 0.68 μM, 0.04 to 12.95 nmol/mg/min, and 0.06 to 109.60 ml/mg/min, respectively. To model UGT1A9-mediated glucuronidation, 30 flavonols were split into the training (23 compounds) and test (7 compounds) sets. These flavonols were then aligned by mapping the flavonols to specific common feature pharmacophores, which were used to construct CoMFA models of V max and CLint, respectively. The derived CoMFA models possessed good internal and external consistency and showed statistical significance and substantive predictive abilities ( V max model: q 2 = 0.738, r 2 = 0.976, r pred2 = 0.735; CLint model: q 2 = 0.561, r 2 = 0.938, rpred2 = 0.630). The contour maps derived from CoMFA modeling clearly indicate structural characteristics associated with rapid or slow 3-O-glucuronidation. In conclusion, the approach of coupling CoMFA analysis with a pharmacophore-based structural alignment is viable for constructing a predictive model for regiospecific glucuronidation rates of flavonols by UGT1A9.

  葡糖醛酸化通常被认为是限制类黄酮醇生物利用度的决定速率的因素之一。因此，利用类黄酮醇的动力学参数（如 Km、Vmax、内在清除率（CLint）= Vmax/ Km）建立葡糖醛酸化的预测模型，将有利于设计合成更多生物可利用的类黄酮醇。本文旨在构建针对3-OH位点的特定比较分子场分析（CoMFA）模型，描述UDP-葡糖醛酸基转移酶（UGT）1A9介导的类黄酮醇葡糖醛酸化过程，该模型可用于设计不佳的UGT1A9底物。我们对重组UGT1A9介导的30种类黄酮醇的3-O-葡糖醛酸化动力学进行了表征，并获得了动力学参数（Km、Vmax、CLint）。观察到的3-O-葡糖醛酸化Km、Vmax和CLint值分别在0.04至0.68 μM、0.04至12.95 nmol/mg/min和0.06至109.60 ml/mg/min之间。为了模拟UGT1A9介导的葡糖醛酸化，我们将30种类黄酮醇分为训练集（23个化合物）和测试集（7个化合物）。然后通过将类黄酮醇映射到特定的共同特征药效团来对齐，从而构建了Vmax和CLint的CoMFA模型。得到的CoMFA模型具有良好的内在和外在一致性，显示出统计学意义和实质性的预测能力（Vmax模型：q2 = 0.738，r2 = 0.976，rpred2 = 0.735；CLint模型：q2 = 0.561，r2 = 0.938，rpred2 = 0.630）。从CoMFA建模得到的轮廓图清晰地表明了与快速或慢速3-O-葡糖醛酸化相关的结构特征。总之，结合CoMFA分析和基于药效团的结构对齐方法是可行的，可以构建用于UGT1A9介导的类黄酮醇区域特异性葡糖醛酸化速率的预测模型。
• Convenient syntheses of metabolically important quercetin glucuronides and sulfates
  作者：Paul W. Needs、Paul A. Kroon

  DOI：10.1016/j.tet.2006.04.102

  日期：2006.7

  Synthetic approaches to the major human plasma metabolites of quercetin, quercetin 3'-sulfate and the beta-D-glucopyranosiduronic acid derivatives 3'-methylquercetin 3-glucuronide (isorhamnetin 3-glucuronide), quercetin 3-glucuronide and quercetin 3'-glucuronide are described. This is the first report of the chemical synthesis of quercetin 3'-glucuronide. All procedures start from the same precursor, 4',7-di-O-benzylquercetin, and all are more convenient than existing methods. (c) 2006 Elsevier Ltd. All rights reserved.