β-D-glucopyranose-1,2,3,4,6-pentakis[3,4-bis(phenylmethoxy)benzoate]

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 单宁
• 英文名称: β-D-glucopyranose-1,2,3,4,6-pentakis[3,4-bis(phenylmethoxy)benzoate]
• 英文别名: 1,2,3,4,6-pentakis[O-(3,4-dibenzyloxybenzoyl)]-β-D-glucopyranoside；[(2R,3R,4S,5R,6S)-3,4,5,6-tetrakis[[3,4-bis(phenylmethoxy)benzoyl]oxy]oxan-2-yl]methyl 3,4-bis(phenylmethoxy)benzoate
• 化学式: C₁₁₁H₉₂O₂₁
• 分子量: 1761.94
• InChiKey: PNWWGBYKQCFLBN-XGAIUSHTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  22.7
• 重原子数：
  132
• 可旋转键数：
  46
• 环数：
  16.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  233
• 氢给体数：
  0
• 氢受体数：
  21

反应信息

• 作为反应物：
  描述：

  β-D-glucopyranose-1,2,3,4,6-pentakis[3,4-bis(phenylmethoxy)benzoate] 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以82.1%的产率得到1,2,3,4,6-pentakis[O-(3,4-dihydroxybenzoyl)]-β-D-glucopyranoside
  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
• 作为产物：
  描述：

  a-无水葡萄糖酯 、 3,4-二(苄氧基)苯甲酸 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以8.6%的产率得到α-D-glucopyranose-1,2,3,4,6-pentakis[3,4-bis(phenylmethoxy)benzoate]
  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

• 1,2,3,4,6-Pentakis[-O-(3,4,5-trihydroxybenzoyl)]-α,β-D-glucopyranose (PGG) analogs: design, synthesis, anti-tumor and anti-oxidant activities
  作者：Qurat-ul-ain Shaikh、Meiting Yang、Khadim Hussain Memon、Mehreen Lateef、Du Na、Shengbiao Wan、Deslandes Eric、Lijuan Zhang、Tao Jiang

  DOI：10.1016/j.carres.2016.04.021

  日期：2016.7

  HT29 and H1299 cells with IC50 of 1.76 µM and 3.65 µM, respectively, indicating the mutual contribution of m-methoxy and p-hydroxy groups to the observed cytotoxicities. Moreover, cinnamic acid analogs were less active than the benzoic acid analogs evidenced by higher IC50 values. Furthermore, in cinnamic acid analogs the hydrogenation of double bond to saturated 2-C side chain enhance the cytotoxicities

  1,2,3,4,6-五[[O-（（3,4,5-三羟基苯甲酰基）]-α，β-D-吡喃葡萄糖（PGG）12的抗氧化活性已有报道，其中游离的OH基团在PGG中似乎对活动至关重要。为了探索基于PGG的化合物作为化学治疗剂并分析PGG中特定OH基团对抗癌活性的贡献，我们设计并合成了27种PGG苯甲酸和肉桂酸类似物。测试了这些类似物对两种人肺（A549和H1299）和两种人结肠（HCT116和HT29）癌细胞系的细胞毒性。化合物12（PGG）对HCT116和A549细胞具有最高的细胞毒性，IC50分别为1.61 µM和3.02 µM。相反，化合物16（1,2,3,4,6-戊基[-O-（4-羟基-3-甲氧基苯甲酰基）]-α，β-D-吡喃葡萄糖，PVG）最有效地杀死HT29和H1299细胞，IC50分别为1.76 µM和3.65 µM，表明间甲氧基和对羟基对观察到的细胞毒性具有相互影响。而且，肉桂酸类似物
• [EN] GP120 -BINDING BENZENE COMPOUNDS AND SACCHARIDE COMPOUNDS<br/>[FR] COMPOSÉS DE BENZÈNES ET DE SACCHARIDES SE LIANT À GP120
  申请人：UNIV LEUVEN KATH

  公开号：WO2011085454A1

  公开（公告）日：2011-07-21

  The present invention provides for novel benzene compounds and saccharide compounds and for the use of said compounds for binding, titration (quantification), removing, purifying or separating the glycoprotein gp120, gp120 comprising viruses or cells infected with gp120 comprising viruses. The invention also provides for a method for the detection, binding, titration (quantification), removal, purification or separation of (or directing therapeutic or other agents to) gp120, gp120 comprising viruses or cells infected with gp120 comprising viruses. The invention further provides for the use of the compounds and for methods using the compounds for directing anti -viral drugs or other agents to gp120 comprising viruses or to gp120 comprising virus - infected cells. The present invention also provides processes for the preparation of said novel compounds.

  本发明提供了新型苯化合物和糖化合物，并用于结合、滴定（定量）、去除、纯化或分离含有糖蛋白gp120的化合物的用途，该gp120包括病毒或感染有包含gp120病毒的细胞。本发明还提供了一种用于检测、结合、滴定（定量）、去除、纯化或分离（或将治疗或其他药物引导至）gp120的方法，该gp120包括病毒或感染有包含gp120病毒的细胞。本发明进一步提供了利用这些化合物的用途，以及用于将抗病毒药物或其他药物引导至含有gp120的病毒或含有gp120病毒感染细胞的方法。本发明还提供了用于制备这些新型化合物的工艺。
• METHODS AND COMPOSITIONS FOR TREATING DIABETES MELLITIS
  申请人：Ohio University

  公开号：EP1545554A1

  公开（公告）日：2005-06-29
• EP1545554A4
  申请人：——

  公开号：EP1545554A4

  公开（公告）日：2006-06-14
• Methods and compositions for treating diabetes mellitis
  申请人：Chen Xiaozhuo

  公开号：US20060058243A1

  公开（公告）日：2006-03-16

  Methods for modulating diabetes, impaired glucose tolerance, gestational diabetes and glucose resistance in a mammal, particularly a human. In one embodiment the method comprises administering a gallotannin composition to a mammal in need of the same. The gallotannin composition comprises one or more select hydrolysable gallotannins. In another embodiment the method comprises administering a gallotannin variant composition comprising one ore more select gallotannin variant compounds to the subject. Methods of preventing or treating weight gain in a subject. The method comprises administering the gallotannin composition of the present invention, the gallotannin variant composition of the present invention, or a combination of the gallotannin composition of the present invention and the gallotannin variant composition of the present invention to the subject. The present invention also relates a gallotannin variant compound or a salt thereof, and a pharmaceutical composition comprising such compound or the salt thereof.