1,2,3,4,6-pentakis-O-(3’,4’,5’-tribenzyloxybenzoyl)-α-D-glucopyranose | 70424-95-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 单宁
• 英文名称: 1,2,3,4,6-pentakis-O-(3’,4’,5’-tribenzyloxybenzoyl)-α-D-glucopyranose
• 英文别名: α-D-glucopyranose-1,2,3,4,6-pentakis[3,4,5-tris(phenylmethoxy)benzoate]；α-D-glucopyranose pentakis[3,4,5-tris(phenylmethoxy)benzoate]；1,2,3,4,6-penta-O-(3,4,5-tri-O-benzylgalloyl)-α-D-glucopyranose；[(2R,3R,4S,5R,6R)-3,4,5,6-tetrakis[[3,4,5-tris(phenylmethoxy)benzoyl]oxy]oxan-2-yl]methyl 3,4,5-tris(phenylmethoxy)benzoate
• CAS: 70424-95-2
• 化学式: C₁₄₆H₁₂₂O₂₆
• 分子量: 2292.56
• InChiKey: DXBOPZWOODFFKH-MCRHMESRSA-N

物化性质

• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  30
• 重原子数：
  172
• 可旋转键数：
  61
• 环数：
  21.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  279
• 氢给体数：
  0
• 氢受体数：
  26

反应信息

• 作为反应物：
  描述：

  1,2,3,4,6-pentakis-O-(3’,4’,5’-tribenzyloxybenzoyl)-α-D-glucopyranose 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以90%的产率得到1,2,3,4,6-penta-O-galloyl-α-D-glucose
  参考文献：
  名称：

  天然产物的高效全合成，以及不自然

  摘要：

  天然产物的合成短（8）， （10）和非天然（13）是基于所述苄没食子酸的高效酯化反应达到5与α，β-吡喃葡萄糖11和4分别。

  DOI：

  10.1016/s0040-4020(97)00702-3
• 作为产物：
  描述：

  a-无水葡萄糖酯 、 3,4,5-tris(benzyloxy)benzoyl chloride 在 4-二甲氨基吡啶 作用下， 以 乙腈 为溶剂， 反应 18.0h， 生成 1,2,3,4,6-pentakis-O-(3’,4’,5’-tribenzyloxybenzoyl)-α-D-glucopyranose
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship Study of Antidiabetic Penta-O-galloyl-d-glucopyranose and Its Analogues

  摘要：

  The rapid increase of obesity-associated diabetes has created urgent demands for more effective antidiabetic therapies and pharmaceuticals that are able to address the problems of hyperglycemia and weight gain simultaneously. Our previous studies indicated that the alpha- and beta-anomers of penta-O-galloyl-D-glucopyranose (PGG), 2 and 3, act as insulin mimetics that bind to and activate the insulin receptor, stimulate glucose transport in adipocytes, and reduce blood glucose and insulin levels in diabetic and obese animals. In addition, they inhibit differentiation of preadipocytes into adipocytes. These activities suggest that 2 and 3 may reduce blood glucose without increasing adiposity. To investigate the structure-activity relationship of 2 and 3, four series of novel compounds were prepared and their glucose transport stimulatory activities were measured using a radioactive glucose uptake bioassay. The assay results indicate that both the glucose and the galloyl groups are critical to the activity of 2 and 3. It appears that the glucose core provides an optimal scaffold to present the galloyl groups with the correct spatial orientation to induce activity. Moreover, the galloyl groups linked to the 1, 2, 3, and 4 positions of glucose are essential, while the galloyl group connected to the 6 position of 2 is unnecessary for the induction of activity. The discovery that two related novel compounds, 6-deoxytetra-O-galloyl-alpha-D-glucopyranose (43) and tetra-O-galloyl-alpha-D-xylopyranose (59), also possess glucose transport stimulatory activity suggests that 2 may be further modified around position 6 to modulate and enhance its efficacy. To test this hypothesis, we developed a new synthetic method that allows for the stereoselective preparation of derivatives of 2 that are modified on C-6. We found that 6-chloro-6-deoxy- 1,2,3,4-tetra-O-galloyl-alpha-D-glucopyranose (80) exhibits a significantly higher glucose transport stimulatory activity than 2. Its activity is comparable to that of insulin.

  DOI：

  10.1021/jm060087k

文献信息

• Gallotannins and Tannic Acid: First Chemical Syntheses and In Vitro Inhibitory Activity on Alzheimer’s Amyloid β-Peptide Aggregation
  作者：Tahiri Sylla、Laurent Pouységu、Grégory Da Costa、Denis Deffieux、Jean-Pierre Monti、Stéphane Quideau

  DOI：10.1002/anie.201411606

  日期：2015.7.6

  against Alzheimer’s disease has unveiled several plant polyphenols that are capable of inhibiting the formation of toxic β‐amyloid fibrils. Gallic acid based gallotannins are among these polyphenols, but their antifibrillogenic activity has thus far been examined using “tannic acid”, a commercial mixture of gallotannins and other galloylated glucopyranoses. The first total syntheses of two true gallotannins

  在寻找对抗阿尔茨海默氏病的新先导化合物的过程中，对天然产物的筛选揭示了几种能够抑制有毒β-淀粉样蛋白原纤维形成的植物多酚。在这些多酚中有基于没食子酸的没食子鞣质，但是迄今为止，已经使用“鞣酸”（一种鞣花酸和其他没食子酰化吡喃葡萄糖的商业混合物）检查了它们的抗原纤维形成活性。现在描述两种真实的没食子鞣质，六没食子酰基吡喃葡萄糖和十加铝基化的化合物的首次总合成，该化合物的结构通常用于描绘“鞣酸”。这些去甲没食子鞣质和更简单的没食子酸酯化的葡萄糖衍生物均在体外抑制淀粉样蛋白β肽（Aβ）的聚集，并且单没食子酸酯化的α-葡糖醇和天然β-六没糖基葡萄糖被证明是最强的抑制剂。
• Synthesis and Antitumor Activity of Ellagic Acid Peracetate
  作者：Yulin Ren、Min Wei、Patrick C. Still、Shunzong Yuan、Youcai Deng、Xiaozhuo Chen、Klaus Himmeldirk、A. Douglas Kinghorn、Jianhua Yu

  DOI：10.1021/ml300065z

  日期：2012.8.9

  Ellagic acid (1) was synthesized for the first time from methyl gallate through a-pentagalloylglucose (alpha-PGG), and ellagic acid peracetate (3,4,3',4'-tetra-O-acetylellagic acid, 2) was derived from 1 by acetylation. Oral administration of 2 suppressed melanoma growth significantly in C7BL/6 immunocompetent mice without having any effect on natural killer (NK) cell activity. Comparison of the immunoenhancing activities of 1 and 2 indicated that the latter compound increased white blood cell quantities in peripheral blood and immune cells enriched from the bone marrow and liver of mice. Therefore, both the antitumor efficacy and the immunity enhancement by 2 were greater than those by 1. In addition, on oral administration, neither 1 nor 2 resulted in whole body, liver, or spleen weight changes of normal, tumor-free mice, indicating that these compounds are potentially nontoxic to mice. It was shown that ellagic acid peracetate (2) inhibits B16 melanoma cell growth in vitro and induces B16 cell apoptosis, corresponding to BCL-2 down-regulation. Collectively, the present data imply that 2 can suppress tumor growth by enhancing mouse immunity and inducing tumor cell apoptosis without apparent side effects.
• Designing Allosteric Inhibitors of Factor XIa. Lessons from the Interactions of Sulfated Pentagalloylglucopyranosides
  作者：Rami A. Al-Horani、Umesh R. Desai

  DOI：10.1021/jm500311e

  日期：2014.6.12

  We recently introduced sulfated pentagalloylglucopyranoside (SPGG) as an allosteric inhibitor of factor XIa (FXIa) (Al-Horani et al., J. Med Chem. 2013, 56, 867-878). To better understand the SPGG-FXIa interaction, we utilized eight SPGG variants and a range of biochemical techniques. The results reveal that SPGG's sulfation level moderately affected FXIa inhibition potency and selectivity over thrombin and factor Xa. Variation in the anomeric configuration did not affect potency. Interestingly, zymogen factor XI bound SPGG with high affinity, suggesting its possible use as an antidote. Acrylamide quenching experiments suggested that SPGG induced significant conformational changes in the active site of FXIa. Inhibition studies in the presence of heparin showed marginal competition with highly sulfated SPGG variants but robust competition with less sulfated variants. Resolution of energetic contributions revealed that nonionic forces contribute nearly 87% of binding energy suggesting a strong possibility of specific interaction. Overall, the results indicate that SPGG may recognize more than one anion-binding, allosteric site on FXIa. An SPGG molecule containing approximately 10 sulfate groups on positions 2 through 6 of the pentagalloylglucopyranosyl scaffold may be the optimal FXIa inhibitor for further preclinical studies.
• [EN] AN EFFICIENT METHOD TO SYNTHESIZE BENZYL GROUP-PROTECTED ALPHA-PENTAGALLOYLGLUCOSE (Alpha-PGG) AND ITS ANALOGUES<br/>[FR] PROCEDE EFFICACE DE SYNTHESE D'ALPHA-PENTAGALLOYLGLUCOSE ( DOLLAR G(A)-PGG) PROTEGE PAR UN GROUPE BENZYLE ET SES ANALOGUES
  申请人：UNIV OHIO

  公开号：WO2005072765A3

  公开（公告）日：2005-09-29
• Anomeric selectivity in the synthesis of galloyl esters of d-glucose
  作者：Robert C. Binkley、Jessica C. Ziepfel、Klaus B. Himmeldirk

  DOI：10.1016/j.carres.2008.10.024

  日期：2009.1

  The anomeric selectivity of the ester formation between D-glucopyranose and gallic acid was investigated under a variety of conditions. A new protocol was established that allows performing the reaction under conditions where mutarotation is very slow. Highly alpha- or beta-selective transformations are possible when starting with alpha- or beta-D-glucopyranose, respectively. Due to the kinetic anomeric effect, a high (x-selectivity is more difficult to achieve than a high beta-selectivity. The new methodology presented in this article was compared with established procedures for the synthesis of gallotannins. In addition to the advantages of a high yield and an easy purification protocol, the new procedure uniquely allowed for a highly selective synthesis of alpha-products. (C) 2008 Elsevier Ltd. All rights reserved.