1-(4,6-bis(benzyloxy)-2-hydroxy-3-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-yl)phenyl)ethanone | 169566-46-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4,6-bis(benzyloxy)-2-hydroxy-3-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-yl)phenyl)ethanone
• 英文别名: 4,6-bis(benzyloxy)-2-hydroxy-3-C-β-D-(2,3,4,6-tetra-O-benzylglucopyranosyl)acetophenone；4,6-bis-benzyloxy-3-C-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-2-hydroxyacetophenone；2,4-dibenzyloxy-6-hydroxy-5-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)acetophenone；2,6-di-O-benzyl-3-C-β-D-(2,3,4,6-tetra-O-benzyl)glucopyranosylphloroacetophenone；1-[2-hydroxy-4,6-bis(phenylmethoxy)-3-[(2S,3S,4R,5R,6R)-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-yl]phenyl]ethanone
• CAS: 169566-46-5
• 化学式: C₅₆H₅₄O₉
• 分子量: 871.039
• InChiKey: QMJSXQCUPRQRKI-RPRCYPACSA-N

物化性质

• 沸点：
  913.4±65.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  9.8
• 重原子数：
  65
• 可旋转键数：
  21
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-(4,6-bis(benzyloxy)-2-hydroxy-3-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-yl)phenyl)ethanone 在 palladium on activated charcoal 氢气 、 碘 作用下， 以 1,4-二氧六环 、 sodium hydroxide 、 乙醇 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 反应 24.5h， 生成 荭草苷
  参考文献：
  名称：

  8-C-葡萄糖基黄酮的合成。

  摘要：

  Orientin，Parkinsonin A，isoswertiajaponin和Parkinsonin B的合成，它们是8-C-β-D-吡喃葡萄糖基-3'，4'，5,7-四羟基黄酮，5-甲基Orientin，7-甲基Orientin和5在此分别报道了7，7-二甲基东方蛋白。通过区域和立体选择性的O→C糖基重排获得C-葡萄糖基苯乙酰苯酮衍生物。C-葡糖基苯乙酮衍生物与3，4-双苄氧基苯甲醛的醛醇缩合得到相应的C-葡糖基查耳酮。通过与I（2）-Me（2）SO反应来构建黄酮系统，然后消除黄酮结构中的5-苄基保护基团，从而得到orientin衍生物和isoswertiajaponin衍生物。Orientin衍生物与硫酸二甲酯的甲基化反应产生了Parkinsonin A衍生物，isoswertiajaponin衍生物和parkinsonin B衍生物。最后，这些C-葡糖基黄酮衍生物的氢解产生了四个

  DOI：

  10.1016/s0008-6215(01)00192-6
• 作为产物：
  描述：

  甲基-Alpha-D-吡喃葡糖苷 在 三氟甲磺酸三甲基硅酯 、 硫酸 、 sodium hydride 、 potassium carbonate 、 溶剂黄146 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 54.17h， 生成 1-(4,6-bis(benzyloxy)-2-hydroxy-3-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-yl)phenyl)ethanone
  参考文献：
  名称：

  Exploiting the Therapeutic Potential of 8-β-d-Glucopyranosylgenistein: Synthesis, Antidiabetic Activity, and Molecular Interaction with Islet Amyloid Polypeptide and Amyloid β-Peptide (1–42)

  摘要：

  8-β-d-Glucopyranosylgenistein (1), the major component of Genista tenera, was synthesized and showed an extensive therapeutical impact in the treatment of STZ-induced diabetic rats, producing normalization of fasting hyperglycemia and amelioration of excessive postprandial glucose excursions and and increasing β-cell sensitivity, insulin secretion, and circulating insulin within 7 days at a dose of 4 (mg/kg bw)/day. Suppression of islet amyloid polypeptide (IAPP) fibril formation by compound 1 was demonstrated by thioflavin T fluorescence and atomic force microscopy. Molecular recognition studies with IAPP and Aβ1-42 employing saturation transfer difference (STD) confirmed the same binding mode for both amyloid peptides as suggested by their deduced epitope. Insights into the preferred conformation in the bound state and conformers' geometry resulting from interaction with Aβ1-42 were also given by STD, trNOESY, and MM calculations. These studies strongly support 8-β-d-glucopyranosylgenistein as a promising molecular entity for intervention in amyloid events of both diabetes and the frequently associated Alzheimer's disease.

  DOI：

  10.1021/jm501069h

文献信息

• Practical Synthesis of a<i>C</i>-Glycosyl Flavonoid via<i>O</i>→<i>C</i>Glycoside Rearrangement
  作者：Toshihiro Kumazawa、Kazuhito Ohki、Mitsuo Ishida、Shingo Sato、Jun-ichi Onodera、Shigeru Matsuba

  DOI：10.1246/bcsj.68.1379

  日期：1995.5

  The C-glycosylation of 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl fluoride and 2-acetylphloroglucinol 3,5-bis(alkyl ether) in the presence of boron trifluoride etherate as an activator stereoselectively gave the β-C-glucoside in a good yield via O → C glycoside rearrangement. Subsequently, aldol condensation of the C-glucoside with benzaldehyde afforded the corresponding β-C-glucosyl chalcone in a good

  2,3,4,6-四-O-苄基-α-D-吡喃葡萄糖基氟和2-乙酰间苯三酚3,5-双（烷基醚）在三氟化硼醚化物作为活化剂存在下的C-糖基化立体选择性地得到通过 O → C 糖苷重排，β-C-糖苷的产率很高。随后，C-葡萄糖苷与苯甲醛的羟醛缩合以良好的收率提供相应的β-C-葡萄糖基查耳酮。
• 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。
• Glucose uptake enhancing activity of puerarin and the role of C-glucoside suggested from activity of related compounds
  作者：Eisuke Kato、Jun Kawabata

  DOI：10.1016/j.bmcl.2010.06.077

  日期：2010.8

  Chemical treatment of diabetes mellitus is widely studied and controlling of blood glucose level is the main course of therapy. In type 2 diabetes mellitus, insulin resistance is the major problem. An isoflavone C-glucoside, puerarin (1), is known to enhance glucose uptake into the insulin sensitive cell and is thought to be a candidate for treatment of diabetes mellitus. We synthesized 1 and several

  对糖尿病的化学治疗进行了广泛的研究，控制血糖水平是治疗的主要过程。在2型糖尿病中，胰岛素抵抗是主要问题。已知异黄酮C-葡萄糖苷，葛根素（1）可增强葡萄糖对胰岛素敏感性细胞的吸收，并被认为是治疗糖尿病的候选药物。我们合成了1种和几种衍生物，用于结构-活性关系研究。针对3T3-L1脂肪细胞的结果表明，在体外测试时，1的C-糖苷部分并不关心其活性，而负责其活性的主要结构是异黄酮部分。
• Targeting Type 2 Diabetes with <i>C</i>-Glucosyl Dihydrochalcones as Selective Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors: Synthesis and Biological Evaluation
  作者：Ana R. Jesus、Diogo Vila-Viçosa、Miguel Machuqueiro、Ana P. Marques、Timothy M. Dore、Amélia P. Rauter

  DOI：10.1021/acs.jmedchem.6b01134

  日期：2017.1.26

  Inhibiting glucose reabsorption by sodium glucose co-transporter proteins (SGLTs) in the kidneys is a relatively new strategy for treating type 2 diabetes. Selective inhibition of SGLT2 over SGLT1 is critical for minimizing adverse side effects associated with SGLT1 inhibition. A library of C-glucosyl dihydrochalcones and their dihydrochalcone and chalcone precursors was synthesized and tested as SGLT1/SGLT2

  通过钠葡萄糖共转运蛋白（SGLT）抑制肾脏中的葡萄糖重吸收是治疗2型糖尿病的一种相对较新的策略。相对于SGLT1而言，对SGLT2的选择性抑制对于最小化与SGLT1抑制相关的不利副作用至关重要。合成了C-葡萄糖基二氢查耳酮及其二氢查耳酮和查耳酮前体的文库，并使用基于细胞的葡萄糖吸收荧光测定法测试了它们作为SGLT1 / SGLT2抑制剂的能力。SGLT2的最有效抑制剂（IC 50 = 9–23 nM）是SGLT1的较弱抑制剂（IC 50）= 10–19μM）。他们对葡萄糖转运蛋白的钠依赖性GLUT家族没有影响，最有效的对培养细胞没有急性毒性。通过计算对C-葡萄糖基二氢查耳酮与POPC膜的相互作用进行了建模，从而提供了它不是泛测定干扰化合物的证据。这些结果指向发现是有效且高度选择性的SGLT2抑制剂的结构。
• Conversion of β-d-C-glucopyranosyl phloroacetophenone to a spiroketal compound
  作者：Toshihiro Kumazawa、Nobutaka Asahi、Shigeru Matsuba、Shingo Sato、Kimio Furuhata、Jun-ichi Onodera

  DOI：10.1016/s0008-6215(98)00067-6

  日期：1998.3

  Abstract Treatment of β- d -C-glucopyranosyl phloroacetophenone in water in the presence of a catalytic amount of p-TsOH afforded a spiroketal product. This is the first demonstration of ring conversion in aryl C-glycoside. The structure of the product was determined by 1H-1H COSY, HMQC, HMBC, NOESY, and single crystal X-ray analysis of the corresponding acetylated compound.

  摘要在催化量的p-TsOH存在下，对水中的β-d-C-吡喃葡萄糖基苯乙酮进行处理，得到了螺酮体产品。这是在芳基C-糖苷中环转化的首次证明。通过1H-1H COSY，HMQC，HMBC，NOESY以及相应乙酰化化合物的单晶X射线分析确定产物的结构。