2-(3,4二羟基苯基)-5,7-二羟基-4-氧代-4H-1-苯并吡喃-3-基-beta-D-吡喃葡糖苷酸 | 22688-79-5

• 物质功能分类: 分析化学 - 分析试剂 - 离子色谱试剂
• 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: 2-(3,4二羟基苯基)-5,7-二羟基-4-氧代-4H-1-苯并吡喃-3-基-beta-D-吡喃葡糖苷酸
• 中文别名: 2-(3,4二羟基苯基)-5,7-二羟基-4-氧代-4H-1-苯并吡喃-3-基-BETA-D-吡喃葡糖苷酸
• 英文名称: quercetin 3-O-β-D-glucuronopyranoside
• 英文别名: quercetin 3-O-β-D-glucopyranosiduronic acid；quercetin 3-O-β-D-glucoronopyranoside；quercetin-3-O-β-D-glucuronopyranoside；3-O-β-D-glucopyranuronosylquercetin；quercetin 3-O-β-D-glucopyranuronide；quercetin 3-O-β-D-glucuropyranoside；Querciturone；(2S,3S,4S,5R,6S)-6-[2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxochromen-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid
• CAS: 22688-79-5
• 化学式: C₂₁H₁₈O₁₃
• 分子量: 478.366
• InChiKey: DUBCCGAQYVUYEU-ZUGPOPFOSA-N

物化性质

• 熔点：
  193～195℃
• 沸点：
  927.8±65.0 °C(Predicted)
• 密度：
  1.96±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）
• LogP：
  2.100 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  224
• 氢给体数：
  8
• 氢受体数：
  13

安全信息

• 安全说明：
  S24/25
• WGK Germany：
  3

制备方法与用途

简介

槲皮素3-O-葡萄糖酸苷是一种黄酮类化合物，存在于春柴胡中。春柴胡为江苏和安徽部分地区春季采收的狭叶柴胡带根全草。

制备

将含有特定基因的大肠杆菌过夜培养物接种到含适当抗生素的新鲜LB培养基中。加入1 mM IPTG后，在18°C下再培养转化体20小时。通过离心收获细胞，并重新悬浮在含2%葡萄糖、抗生素以及1mM IPTG的新鲜M9培养基中。将细胞密度调整为OD600值为2。保持总反应体积2 mL的试管中，加入一百微摩尔的木犀草素，在25°C下孵育1.5小时后，再添加100 μM木犀草素并继续孵育1.5小时。将混合物中的木犀草素浓度调整为200 μM，并在反应开始后2小时再次加入。保持反应混悬液2小时后，将细胞密度调整为OD600值为3，然后加入200 μM槲皮素，孵育2小时。最终产物为2-(3,4-二羟基苯基)-5,7-二羟基-4-氧代-4H-1-苯并吡喃-3-基-BETA-D-吡喃葡糖苷酸。

生物活性

Miquelianin (Quercetin 3-O-glucuronide) 是槲皮素和一种天然类黄酮的代谢产物，具有抗氧化作用。在人血浆中，50 μM 的 miquelianin 显著抑制了番茄红素、β-胡萝卜素和 α-生育酚三种抗氧化剂的消耗。体外研究表明，miquelianin 能够从小肠到达中枢神经系统，并能显著减少来自 Tg2576 AD 小鼠模型的主要神经元培养物中 β-淀粉样蛋白 (Aβ) 片段的生成，还能干扰 Aβ1–40 和 Aβ1–42 初始蛋白质-蛋白质相互作用，这种相互作用是形成神经毒性寡聚体 Aβ 物种所必需的。用 0.1 μM miquelianin 治疗可抑制 ROS 生成、cAMP 和 RAS 激活以及 ERK1/2 磷酸化，并抑制 HMOX1、MMP2 和 MMP9 基因的表达，减少 MDA-MB-231 乳腺癌细胞的侵袭并抑制 MMP-9 的诱导。此外，miquelianin 还能抑制 [3H]-NA 对 b2-AR 的结合，可能通过控制 b2-腺苷受体信号传导来抑制乳腺癌细胞的侵袭，并且可能是缓解应激相关乳腺癌的饮食化学预防因子。

体内研究

与对照组相比，miquelianin 治疗显著改善了 AD 类型缺陷在海马区基底突触传递和长期强化方面的表现。从百里香提取物中获得的一种黄酮类化合物在强迫游泳测试中表现出显著活性，而 miquelianin 是该分离成分之一。

化学性质

棕色结晶性粉末，可溶于甲醇、乙醇、DMSO 等有机溶剂，来源于翻白叶、杠板归和春柴胡。

用途

抗氧化，抗动脉粥样硬化的作用。 用于含量测定/鉴定/药理实验等。

反应信息

• 作为反应物：
  描述：

  2-(3,4二羟基苯基)-5,7-二羟基-4-氧代-4H-1-苯并吡喃-3-基-beta-D-吡喃葡糖苷酸 生成 槲皮素
  参考文献：
  名称：

  ISHIMATSU, MAKOTO;TANAKA, TAKASHI;NONAKA, GEN-ICHIRO;NISHIOKA, ITSUO, PHYTOCHEMISTRY, 28,(1989) N1, C. 3179-3184

  摘要：

  DOI：
• 作为产物：
  描述：

  在 20 % Pd(OH)2/C 、 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 12.0h， 以16 mg的产率得到2-(3,4二羟基苯基)-5,7-二羟基-4-氧代-4H-1-苯并吡喃-3-基-beta-D-吡喃葡糖苷酸
  参考文献：
  名称：

  Regiospecific synthesis of quercetin O-β-d-glucosylated and O-β-d-glucuronidated isomers

  摘要：

  Quercetin, the polyphenolic compound, which has the highest daily intake, is well known for its protective effects against aging diseases and has received a lot of attention for this reason. Both quercetin 3-O-beta-D-glucuronide and quercetin 3'-O-beta-D-glucuronide are human metabolites, which, together with their regioisomers, are required for biological as well as physical chemistry studies. We present here a novel synthetic route based on the sequential and selective protections of the hydroxyl functions of quercetin allowing selective glycosylation, followed by TEMPO-mediated oxidation to the glucuronide. This methodology enabled us to synthesize the five O-beta-D-glucosides and four O-beta-D-glucuronides of quercetin, including the major human metabolite, quercetin 3-O-beta-D-glucuronide. (C) 2011 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2011.03.110

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。
• Flavonoids of the flowers of tamarix nilotica
  作者：M.A.M. Nawwar、A.M.A. Souleman、J. Buddrus、M. Linscheid

  DOI：10.1016/s0031-9422(00)80549-x

  日期：1984.1

  Abstract The ethyl ester of kaempferol 3-O-β- D -glucuronide, the methyl and ethyl esters of quercetin 3-O-β- D -glucuronide have been isolated from an aqueous acetone extract of the flowers of Tamarix nilotica. In addition kaempferol 3-O-sulphate-7,4′-dimethyl ether and the free aglycones were isolated. The structures were established by routine methods, by FAB-MS and by 13C NMR spectral measurements

  摘要 山柰酚 3-O-β-D-葡萄糖醛酸乙酯、槲皮素 3-O-β-D-葡萄糖醛酸甲酯和乙酯已从柽柳花的丙酮水溶液提取物中分离得到。此外，山奈酚 3-O-sulphate-7,4'-二甲醚和游离苷元被分离出来。通过常规方法、FAB-MS和13C NMR光谱测量确定结构。
• An expeditious synthesis of quercetin 3-O-β-d-glucuronide from rutin
  作者：Mohammed Kajjout、Rajae Zemmouri、Christian Rolando

  DOI：10.1016/j.tetlet.2011.06.108

  日期：2011.9

  We report the synthesis of the major human metabolite of quercetin, quercetin 3-O-β-d-glucuronide, from rutin (quercetin-3-rutinoside), which is commercially available at low cost. This straightforward synthesis is based on the key intermediate 3′,4′,5,7-tetra-O-benzyl-quercetin which is obtained in only two steps by the total benzylation of rutin followed by acid hydrolysis of the rutinoside residue

  我们报道了槲皮素的主要人类代谢产物，槲皮素3- O- β- d-葡萄糖苷酸的合成，得自芦丁（槲皮素-3-芸香糖苷），其价格低廉。这种简单的合成是基于关键中间体3'，4'，5,7-四-O-苄基-槲皮素，该步骤仅通过两步进行，即芦丁的总苄基化，然后通过芸苔苷残基的酸水解即可获得。1-溴-3,4,6-四-O-乙酰基-α- d对游离3羟基的糖基化作用-吡喃葡糖苷产生被保护的葡糖苷。TEMPO介导的脱保护的葡糖苷上伯醇的氧化使人们能够接触到苄基化的葡糖醛酸苷。通过H 2（10％Pd / C）除去保护槲皮素羟基的苄基产生槲皮素3- O- β- d-葡糖醛酸苷。
• Quercetin 3-glucuronide-3′-sulphate from Hypericum elodes
  作者：Rosa M. Seabra、A.Correia Alves

  DOI：10.1016/0031-9422(88)80720-9

  日期：1988.1

  Abstract A new flavonol glycoside isolated from Hypericum elodes has been identified by spectral and chromatographic data as quercetin 3-glucuronide-3′-sulphate.

  摘要 从金丝桃属植物中分离出的一种新的黄酮醇糖苷已通过光谱和色谱数据鉴定为槲皮素 3-葡糖苷酸-3'-硫酸盐。
• The Anti-thrombotic Active Constituents from Centella asiatica
  作者：Toshiko Satake、Kohei Kamiya、Yin An、Tomomi Oishi(nee Taka)、Junichiro Yamamoto

  DOI：10.1248/bpb.30.935

  日期：——

  The in vitro effects of a methanol extract from the aerial parts of Centella asiatica on shear-induced platelet activation and coagulation were assessed after oral administration to rats, by subjecting non-anticoagulated blood to haemostatometry. 3,5-Di-O-caffeoyl quinic acid, 1,5-di-O-caffeoyl quinic acid, 3,4-di-O-caffeoyl quinic acid, 4,5-di-O-caffeoyl quinic acid, and chlorogenic acid, together with asiaticoside, kaempferol, quercetine, kaempferol-3-O-β-D-glucoside and quercetin-3-O-β-D-glucoside were all isolated from the methanol extract. Amongst these, only 3,5-di-O-caffeoylquinic acid showed significant inhibition of shear-induced platelet activation and dynamic coagulation. The reactive curve of the inhibitory effect on the platelet reaction and the dynamic coagulation showed a bell-shape.

  大鼠口服积雪草气生部分的甲醇提取物后，通过对无抗凝血的血液进行止血测定，评估了该提取物对剪切力诱导的血小板活化和凝血的体外效应。3,5-二-O-咖啡酰基奎宁酸、1,5-二-O-咖啡酰基奎宁酸、3,4-二-O-咖啡酰基奎宁酸、4,5-二-O-咖啡酰基奎宁酸、绿原酸以及积雪草苷、从甲醇提取物中分离出了山柰酚、槲皮素、山柰-3-O-β-<小>D-葡萄糖苷和槲皮素-3-O-β-<小>D-葡萄糖苷。其中，只有 3,5-二-O-咖啡酰奎宁酸对剪切力诱导的血小板活化和动态凝血有明显的抑制作用。对血小板反应和动态凝血抑制作用的反应曲线呈钟形。