2-(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyloxy)phenol | 1092527-96-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyloxy)phenol
• 英文别名: 2-[(2R,3R,4S,5R,6R)-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-yl]oxyphenol
• CAS: 1092527-96-2
• 化学式: C₄₀H₄₀O₇
• 分子量: 632.753
• InChiKey: MCGAREXNKNWTPQ-DTQLOPILSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  47
• 可旋转键数：
  15
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  75.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyloxy)phenol 在 咪唑 、 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 氢气 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 92.0h， 生成 2-(α-D-glucopyranosyloxy)phenyl benzoate
  参考文献：
  名称：

  Glucosylpolyphenols as Inhibitors of Aβ-Induced Fyn Kinase Activation and Tau Phosphorylation: Synthesis, Membrane Permeability, and Exploratory Target Assessment within the Scope of Type 2 Diabetes and Alzheimer’s Disease

  摘要：

  Despite the rapidly increasing number of patients suffering from type 2 diabetes, Alzheimer's disease, and diabetes-induced dementia, there are no disease-modifying therapies that are able to prevent or block disease progress. In this work, we investigate the potential of nature-inspired glucosylpolyphenols against relevant targets, including islet amyloid polypeptide, glucosidases, and cholinesterases. Moreover, with the premise of Fyn kinase as a paradigm-shifting target in Alzheimer's drug discovery, we explore glucosylpolyphenols as blockers of Aβ-induced Fyn kinase activation while looking into downstream effects leading to Tau hyperphosphorylation. Several compounds inhibit Aβ-induced Fyn kinase activation and decrease pTau levels at 10 μM concentration, particularly the per-O-methylated glucosylacetophloroglucinol and the 4-glucosylcatechol dibenzoate, the latter inhibiting also butyrylcholinesterase and β-glucosidase. Both compounds are nontoxic with ideal pharmacokinetic properties for further development. This work ultimately highlights the multitarget nature, fine structural tuning capacity, and valuable therapeutic significance of glucosylpolyphenols in the context of these metabolic and neurodegenerative disorders.

  DOI：

  10.1021/acs.jmedchem.0c00841
• 作为产物：
  描述：

  alpha-甲基葡萄糖甙 在 calcium sulfate 、 三氟甲磺酸三甲基硅酯 、 硫酸 、 sodium hydride 作用下， 以 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 120.5h， 生成 2-(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyloxy)phenol
  参考文献：
  名称：

  Glucosylpolyphenols as Inhibitors of Aβ-Induced Fyn Kinase Activation and Tau Phosphorylation: Synthesis, Membrane Permeability, and Exploratory Target Assessment within the Scope of Type 2 Diabetes and Alzheimer’s Disease

  摘要：

  Despite the rapidly increasing number of patients suffering from type 2 diabetes, Alzheimer's disease, and diabetes-induced dementia, there are no disease-modifying therapies that are able to prevent or block disease progress. In this work, we investigate the potential of nature-inspired glucosylpolyphenols against relevant targets, including islet amyloid polypeptide, glucosidases, and cholinesterases. Moreover, with the premise of Fyn kinase as a paradigm-shifting target in Alzheimer's drug discovery, we explore glucosylpolyphenols as blockers of Aβ-induced Fyn kinase activation while looking into downstream effects leading to Tau hyperphosphorylation. Several compounds inhibit Aβ-induced Fyn kinase activation and decrease pTau levels at 10 μM concentration, particularly the per-O-methylated glucosylacetophloroglucinol and the 4-glucosylcatechol dibenzoate, the latter inhibiting also butyrylcholinesterase and β-glucosidase. Both compounds are nontoxic with ideal pharmacokinetic properties for further development. This work ultimately highlights the multitarget nature, fine structural tuning capacity, and valuable therapeutic significance of glucosylpolyphenols in the context of these metabolic and neurodegenerative disorders.

  DOI：

  10.1021/acs.jmedchem.0c00841

文献信息

• Carbohydrate-Templated Asymmetric Diels-Alder Reactions of Masked<i>ortho</i>-Benzoquinones for the Synthesis of Chiral Bicyclo[2.2.2]oct-5-en-2-ones
  作者：Shun-Yuan Luo、Yeong-Jiunn Jang、Jing-Yuan Liu、Chrong-Shyua Chu、Chun-Chen Liao、Shang-Cheng Hung

  DOI：10.1002/anie.200802693

  日期：2008.10.6
• Glucosylpolyphenols as Inhibitors of Aβ-Induced Fyn Kinase Activation and Tau Phosphorylation: Synthesis, Membrane Permeability, and Exploratory Target Assessment within the Scope of Type 2 Diabetes and Alzheimer’s Disease
  作者：Ana M. de Matos、M. Teresa Blázquez-Sánchez、Andreia Bento-Oliveira、Rodrigo F. M. de Almeida、Rafael Nunes、Pedro E. M. Lopes、Miguel Machuqueiro、Joana S. Cristóvão、Cláudio M. Gomes、Cleide S. Souza、Imane G. El Idrissi、Nicola A. Colabufo、Ana Diniz、Filipa Marcelo、M. Conceição Oliveira、Óscar López、José G. Fernandez-Bolaños、Philipp Dätwyler、Beat Ernst、Ke Ning、Claire Garwood、Beining Chen、Amélia P. Rauter

  DOI：10.1021/acs.jmedchem.0c00841

  日期：2020.10.22

  Despite the rapidly increasing number of patients suffering from type 2 diabetes, Alzheimer's disease, and diabetes-induced dementia, there are no disease-modifying therapies that are able to prevent or block disease progress. In this work, we investigate the potential of nature-inspired glucosylpolyphenols against relevant targets, including islet amyloid polypeptide, glucosidases, and cholinesterases. Moreover, with the premise of Fyn kinase as a paradigm-shifting target in Alzheimer's drug discovery, we explore glucosylpolyphenols as blockers of Aβ-induced Fyn kinase activation while looking into downstream effects leading to Tau hyperphosphorylation. Several compounds inhibit Aβ-induced Fyn kinase activation and decrease pTau levels at 10 μM concentration, particularly the per-O-methylated glucosylacetophloroglucinol and the 4-glucosylcatechol dibenzoate, the latter inhibiting also butyrylcholinesterase and β-glucosidase. Both compounds are nontoxic with ideal pharmacokinetic properties for further development. This work ultimately highlights the multitarget nature, fine structural tuning capacity, and valuable therapeutic significance of glucosylpolyphenols in the context of these metabolic and neurodegenerative disorders.