4,6-bis-hydroxy-3-C-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-2-hydroxyacetophenone | 1309438-45-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4,6-bis-hydroxy-3-C-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-2-hydroxyacetophenone
• 英文别名: 1-[2,4,6-trihydroxy-3-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)phenyl]ethan-1-one；3-C-(2',3',4',5'-tetra-O-benzyl-β-D-glucopyranosyl)-2,4,6-trihydroxyacetophenone
• CAS: 1309438-45-6
• 化学式: C₄₂H₄₂O₉
• 分子量: 690.79
• InChiKey: ORBHCJVBQOQZIA-VSMVRBPTSA-N

物化性质

• 沸点：
  775.0±60.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.42
• 重原子数：
  51.0
• 可旋转键数：
  15.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  123.91
• 氢给体数：
  3.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  4,6-bis-hydroxy-3-C-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-2-hydroxyacetophenone 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 以93%的产率得到2,4,6-trihydroxyacetophenone 3-C-β-D-glucopyranoside
  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：

  甲基 2,3,4,6-O-四苄基-alpha-D-吡喃葡萄糖苷 在 盐酸 、 溶剂黄146 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 13.0h， 生成 4,6-bis-hydroxy-3-C-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-2-hydroxyacetophenone
  参考文献：
  名称：

  一种氮杂碳苷查尔酮及其制备方法

  摘要：

  本发明提供一种氮杂碳苷查尔酮，其特征在于，所述氮杂碳苷查尔酮包括具有通式Ⅰ或通式Ⅱ的化合物，或者，所述氮杂碳苷查尔酮包括所述通式Ⅰ或通式Ⅱ的化合物与无机酸或有机酸形成的药学可接受的盐，所述氮杂碳苷查尔酮既能够较好的适应工业化生产，并且毒副作用小、降糖效果快，能够更好地缓解糖尿病患者的症状；

  公开号：

  CN110016006B

文献信息

• 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。
• [EN] METHOD FOR THE SYNTHESIS OF ASPALATHIN AND ANALOGUES THEREOF<br/>[FR] PROCÉDÉ DE SYNTHÈSE D'ASPALATHINE ET DE SES ANALOGUES
  申请人：SOUTH AFRICAN MEDICAL RES COUNCIL

  公开号：WO2011064726A1

  公开（公告）日：2011-06-03

  A method of synthesising Aspalathin and its analogues or derivatives is disclosed. The method comprises synthesising a compound of formula 1 or its analogues or derivatives (I) wherein each of R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 is independently selected from the group consisting of -H, -OH, hydrocarbyl groups, saccharide moieties and -OR15; R15 is selected from the group consisting of hydrogen, a hydrocarbyl group (e.g. methoxy or ethoxy), an acyl group and a benzyl group; and R11, R12, R13 and R14 are independently selected from the group consisting of -H, hydrocarbyl groups, saccharide moieties, an acyl group and a benzyl group. The method comprises the step of coupling a sugar to a dihydrochalcone, chalcone or flavanone, or coupling the sugar to an intermediate for producing a dihydrochalcone, chalcone or flavanone followed by coupling of the sugar-intermediate adduct to a further intermediate for producing a dihydrochalcone, chalcone or flavanone, and transforming the product thereof into a compound of formula 1 or an analogue or derivative thereof.

  公开了一种合成Aspalathin及其类似物或衍生物的方法。该方法包括合成式1或其类似物或衍生物（I）的化合物，其中R1、R2、R3、R4、R5、R6、R7、R8、R9和R10中的每一个都是独立地选自-H、-OH、烃基、糖基和-OR15的群组；R15选自氢、烃基（例如甲氧基或乙氧基）、酰基和苄基的群组；R11、R12、R13和R14独立地选自-H、烃基、糖基、酰基和苄基的群组。该方法包括将糖与二氢黄烷酮、黄烷酮或黄酮偶联，或将糖与产生二氢黄烷酮、黄烷酮或黄酮的中间体偶联，然后将糖-中间体加合物与产生二氢黄烷酮、黄烷酮或黄酮的进一步中间体偶联，并将其产物转化为式1或其类似物或衍生物的化合物。
• Method for the Synthesis of Aspalathin and Analogues Thereof
  申请人：Van der Westhuizen Jan Hendrik

  公开号：US20130018182A1

  公开（公告）日：2013-01-17

  A method of synthesising Aspalathin and its analogues or derivatives is disclosed. The method comprises synthesising a compound of formula 1 or its analogues or derivatives: wherein each of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 is independently selected from the group consisting of —H, —OH, hydrocarbyl groups, saccharide moieties and —OR 15 ; R 15 is selected from the group consisting of hydrogen, a hydrocarbyl group (e.g. methoxy or ethoxy), an acyl group and a benzyl group; and R 11 , R 12 , R 13 and R 14 are independently selected from the group consisting of —H, hydrocarbyl groups, saccharide moieties, an acyl group and a benzyl group. The method comprises the step of coupling a sugar to a dihydrochalcone, chalcone or flavanone, or coupling the sugar to an intermediate for producing a dihydrochalcone, chalcone or flavanone followed by coupling of the sugar-intermediate adduct to a further intermediate for producing a dihydrochalcone, chalcone or flavanone, and transforming the product thereof into a compound of formula 1 or an analogue or derivative thereof.

  公开了一种合成Aspalathin及其类似物或衍生物的方法。该方法包括合成式1或其类似物或衍生物的化合物：其中R1、R2、R3、R4、R5、R6、R7、R8、R9和R10中的每一个都是独立选择自羟基、烃基、糖基团和—OR15的群组；R15选择自氢、烃基（例如甲氧基或乙氧基）、酰基和苄基；而R11、R12、R13和R14则独立选择自—H、烃基、糖基团、酰基和苄基的群组。该方法包括将糖与二氢黄烷酮、黄烷酮或黄酮偶联，或将糖与用于产生二氢黄烷酮、黄烷酮或黄酮的中间体偶联，然后将糖-中间体加合物偶联到用于产生二氢黄烷酮、黄烷酮或黄酮的进一步中间体上，并将其转化为式1或其类似物或衍生物的化合物。
• Exploiting the Therapeutic Potential of 8-β-<scp>d</scp>-Glucopyranosylgenistein: Synthesis, Antidiabetic Activity, and Molecular Interaction with Islet Amyloid Polypeptide and Amyloid β-Peptide (1–42)
  作者：Ana R. Jesus、Catarina Dias、Ana M. Matos、Rodrigo F. M. de Almeida、Ana S. Viana、Filipa Marcelo、Rogério T. Ribeiro、Maria P. Macedo、Cristina Airoldi、Francesco Nicotra、Alice Martins、Eurico J. Cabrita、Jesús Jiménez-Barbero、Amélia P. Rauter

  DOI：10.1021/jm501069h

  日期：2014.11.26

  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.