chrysin-8-C-β-D-glucopyranoside | 160880-89-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: chrysin-8-C-β-D-glucopyranoside
• 英文别名: chrysin 8-C-glucoside；5,7-dihydroxy-2-phenyl-8-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]chromen-4-one
• CAS: 160880-89-7
• 化学式: C₂₁H₂₀O₉
• 分子量: 416.384
• InChiKey: PFJBHVURUOQVHW-VPRICQMDSA-N

物化性质

• 沸点：
  716.3±60.0 °C(Predicted)
• 密度：
  1.614±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  157
• 氢给体数：
  6
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  尿苷 5’-二二氧磷基半乳糖二钠盐 、 chrysin-8-C-β-D-glucopyranoside 在 pET28a-(C-glycosyltransferase TcCGT1-2″-O-galactosyltransferase TcOGT4) fusion protein in E.coli BL21(DE3) 作用下， 以 aq. phosphate buffer 为溶剂， 反应 9.0h， 以56%的产率得到chrysin 8-C-β-D-(2''-O-β-D-galactosyl)glucoside
  参考文献：
  名称：

  Characterization of a Highly Selective 2″-O-Galactosyltransferase from Trollius chinensis and Structure-Guided Engineering for Improving UDP-Glucose Selectivity

  摘要：

  DOI：

  10.1021/acs.orglett.1c02581
• 作为产物：
  描述：

  在 吡啶 、 碘 、 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 生成 chrysin-8-C-β-D-glucopyranoside
  参考文献：
  名称：

  Design and Synthesis of CNS-targeted Flavones and Analogues with Neuroprotective Potential Against H2O2- and Aβ1-42-Induced Toxicity in SH-SY5Y Human Neuroblastoma Cells

  摘要：

  由于缺乏能够阻止阿尔茨海默病（AD）进展的药物，发现能够拯救神经元免受细胞损伤的新型神经保护治疗方法目前是极其重要和紧迫的问题。在这里，我们受到自然黄酮类化合物被广泛报道的潜力的启发，建立了一个新型黄酮类化合物、色苷-4-酮及其C-葡萄糖苷衍生物的库，并探索它们作为具有适当药代动力学特性的神经保护剂的能力。所有化合物首先在平行人工膜渗透性测定（PAMPA）中进行评估，以评估它们在生物膜上的有效渗透性，即血脑屏障（BBB）。通过这个测试，我们不仅旨在评估我们的候选者是否分布良好，还要理性地分析糖基对物理化学性质的影响。为了补充我们的分析，还确定了logD7.4。在所有筛选的化合物中，对p-吗啉基黄酮类化合物的能力完全挽救了SH-SY5Y人类神经母细胞瘤细胞免受H2O2和Aβ1-42诱导的细胞死亡。还评估了胆碱酯酶抑制作用，并发现了适度的抑制活性。这项工作突出了C-葡萄糖苷黄酮类化合物作为神经保护剂的潜力，并提出了p-吗啉基C-葡萄糖苷黄酮37，它在100μM时对HepG2和Caco-2细胞没有显示任何细胞毒性，作为进一步针对AD的开发的新的引导结构。

  DOI：

  10.3390/ph12020098

文献信息

• Molecular and Structural Characterization of a Promiscuous <i>C</i> ‐Glycosyltransferase from <i>Trollius chinensis</i>
  作者：Jun‐Bin He、Peng Zhao、Zhi‐Min Hu、Shuang Liu、Yi Kuang、Meng Zhang、Bin Li、Cai‐Hong Yun、Xue Qiao、Min Ye

  DOI：10.1002/anie.201905505

  日期：2019.8.12

  TcCGT1, which is initiated by the spontaneous deprotonation of the substrate. The spacious binding pocket explains the substrate promiscuity, and the binding pose of the substrate determines C‐ or O‐glycosylation activity. Site‐directed mutagenesis at two residues (I94E and G284K) switched C‐ to O‐glycosylation. TcCGT1 is the first plant CGT with a crystal structure and the first flavone 8‐C‐glycosyltransferase

  在本文中，探索了药用植物金莲花（Trollius chinensis）中新的C-糖基转移酶（CGT）TcCGT1的催化混杂性。TcCGT1可以有效和区域特异性地催化36种黄酮和其他类黄酮的8 C糖基化，还可以催化多种酚的O糖基化。TcCGT1与尿苷二磷酸酯复合的晶体结构以1.85Å的分辨率测定。分子对接揭示了TcCGT1催化机制的新模型，该模型由底物的自发去质子化引发。宽大的装订袋说明了基材的混杂性，并且基材的装订姿势决定了C或O糖基化活性。位点定向诱变在两个残基（I94E和G284K）切换Ç -到Ò -glycosylation。TcCGT1是第一个具有晶体结构的植物CGT，并且是第一个描述的黄酮8- C-糖基转移酶。这为设计有效的糖基化生物催化剂提供了基础。
• Biosynthesis of natural and novel C-glycosylflavones utilising recombinant Oryza sativa C-glycosyltransferase (OsCGT) and Desmodium incanum root proteins
  作者：B. Hao、J.C. Caulfield、M.L. Hamilton、J.A. Pickett、C.A.O. Midega、Z.R. Khan、J. Wang、A.M. Hooper

  DOI：10.1016/j.phytochem.2016.02.013

  日期：2016.5

  The rice C-glycosyltransferase (OsCGT) is one of only a small number of characterised plant C-glycosyltransferases (CGT) known. The enzyme C-glucosylates a 2-hydroxyflavanone substrate with UDP-glucose as the sugar donor to produce C-glucosyl-2-hydroxyflavanones. We tested substrate specificity of the enzyme, using synthetic 2-hydroxyflavanones, and showed it has the potential to generate known natural CGFs that have been isolated from rice and also other plants. In addition, we synthesised novel, unnatural 2-hydroxyflavanone substrates to test the B-ring chemical space of substrate accepted by the OsCGT and demonstrated the OsCGT capacity as a synthetic reagent to generate significant quantities of known and novel CGFs. Many B-ring analogues are tolerated within a confined steric limit. Finally the OsCGT was used to generate novel mono-C-glucosyl-2-hydroxyflavanones as putative biosynthetic intermediates to examine the potential of Desmodium incanum biosynthetic CGTs to produce novel di-C-glycosylflavones, compounds implicated in the allelopathic biological activity of Desmodium against parasitic weeds from the Striga genus. (C) 2016 The Authors. Published by Elsevier Ltd.
• Design and Synthesis of CNS-targeted Flavones and Analogues with Neuroprotective Potential Against H2O2- and Aβ1-42-Induced Toxicity in SH-SY5Y Human Neuroblastoma Cells
  作者：Ana M. de Matos、Alice Martins、Teresa Man、David Evans、Magnus Walter、Maria Conceição Oliveira、Óscar López、José G. Fernandez-Bolaños、Philipp Dätwyler、Beat Ernst、M. Paula Macedo、Marialessandra Contino、Nicola A. Colabufo、Amélia P. Rauter

  DOI：10.3390/ph12020098

  日期：——

  With the lack of available drugs able to prevent the progression of Alzheimer’s disease (AD), the discovery of new neuroprotective treatments able to rescue neurons from cell injury is presently a matter of extreme importance and urgency. Here, we were inspired by the widely reported potential of natural flavonoids to build a library of novel flavones, chromen-4-ones and their C-glucosyl derivatives, and to explore their ability as neuroprotective agents with suitable pharmacokinetic profiles. All compounds were firstly evaluated in a parallel artificial membrane permeability assay (PAMPA) to assess their effective permeability across biological membranes, namely the blood-brain barrier (BBB). With this test, we aimed not only at assessing if our candidates would be well-distributed, but also at rationalizing the influence of the sugar moiety on the physicochemical properties. To complement our analysis, logD7.4 was determined. From all screened compounds, the p-morpholinyl flavones stood out for their ability to fully rescue SH-SY5Y human neuroblastoma cells against both H2O2- and Aβ1-42-induced cell death. Cholinesterase inhibition was also evaluated, and modest inhibitory activities were found. This work highlights the potential of C-glucosylflavones as neuroprotective agents, and presents the p-morpholinyl C-glucosylflavone 37, which did not show any cytotoxicity towards HepG2 and Caco-2 cells at 100 μM, as a new lead structure for further development against AD.

  由于缺乏能够阻止阿尔茨海默病（AD）进展的药物，发现能够拯救神经元免受细胞损伤的新型神经保护治疗方法目前是极其重要和紧迫的问题。在这里，我们受到自然黄酮类化合物被广泛报道的潜力的启发，建立了一个新型黄酮类化合物、色苷-4-酮及其C-葡萄糖苷衍生物的库，并探索它们作为具有适当药代动力学特性的神经保护剂的能力。所有化合物首先在平行人工膜渗透性测定（PAMPA）中进行评估，以评估它们在生物膜上的有效渗透性，即血脑屏障（BBB）。通过这个测试，我们不仅旨在评估我们的候选者是否分布良好，还要理性地分析糖基对物理化学性质的影响。为了补充我们的分析，还确定了logD7.4。在所有筛选的化合物中，对p-吗啉基黄酮类化合物的能力完全挽救了SH-SY5Y人类神经母细胞瘤细胞免受H2O2和Aβ1-42诱导的细胞死亡。还评估了胆碱酯酶抑制作用，并发现了适度的抑制活性。这项工作突出了C-葡萄糖苷黄酮类化合物作为神经保护剂的潜力，并提出了p-吗啉基C-葡萄糖苷黄酮37，它在100μM时对HepG2和Caco-2细胞没有显示任何细胞毒性，作为进一步针对AD的开发的新的引导结构。
• Characterization of a Highly Selective 2″-<i>O</i>-Galactosyltransferase from <i>Trollius chinensis</i> and Structure-Guided Engineering for Improving UDP-Glucose Selectivity
  作者：Shuang Liu、Meng Zhang、Yangoujie Bao、Kuan Chen、Lulu Xu、Huifei Su、Yi Kuang、Zilong Wang、Xue Qiao、Min Ye

  DOI：10.1021/acs.orglett.1c02581

  日期：2021.12.3