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

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: α-D-glucopyranose-1,2,3,4,6-pentakis[(4-phenylmethoxy)benzoate]
• 英文别名: 1,2,3,4,6-pentakis[O-(4-benzyloxybenzoyl)]-α-D-glucopyranoside；[(2R,3R,4S,5R,6R)-3,4,5,6-tetrakis[(4-phenylmethoxybenzoyl)oxy]oxan-2-yl]methyl 4-phenylmethoxybenzoate
• 化学式: C₇₆H₆₂O₁₆
• 分子量: 1231.32
• InChiKey: PUFGOQIQGSTWBU-CLVBXFOHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  16.2
• 重原子数：
  92
• 可旋转键数：
  31
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  187
• 氢给体数：
  0
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  α-D-glucopyranose-1,2,3,4,6-pentakis[(4-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76.7%的产率得到[(2R,3R,4S,5R,6R)-3,4,5,6-tetrakis[(4-hydroxybenzoyl)oxy]oxan-2-yl]methyl 4-hydroxybenzoate
  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 、 4-苯甲氧基苯甲酸 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29.2%的产率得到α-D-glucopyranose-1,2,3,4,6-pentakis[(4-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
• Synthesis and Structure−Activity Relationship Study of Antidiabetic Penta-<i>O</i>-galloyl-<scp>d</scp>-glucopyranose and Its Analogues
  作者：Yulin Ren、Klaus Himmeldirk、Xiaozhuo Chen

  DOI：10.1021/jm060087k

  日期：2006.5.1

  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.