2-deoxy-α-D-glucopyranose-1,3,4,6-tetrakis[3,4,5-tris(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: 2-deoxy-α-D-glucopyranose-1,3,4,6-tetrakis[3,4,5-tris(phenylmethoxy)benzoate]
• 英文别名: [(2R,3S,4R,6R)-3,4,6-tris[[3,4,5-tris(phenylmethoxy)benzoyl]oxy]oxan-2-yl]methyl 3,4,5-tris(phenylmethoxy)benzoate
• 化学式: C₁₁₈H₁₀₀O₂₁
• 分子量: 1854.08
• InChiKey: UKXFISRIMGQPGW-CIJPQAEJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  24.3
• 重原子数：
  139
• 可旋转键数：
  49
• 环数：
  17.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  225
• 氢给体数：
  0
• 氢受体数：
  21

反应信息

• 作为反应物：
  描述：

  2-deoxy-α-D-glucopyranose-1,3,4,6-tetrakis[3,4,5-tris(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83%的产率得到[(2R,3S,4R,6R)-3,4,6-tris[(3,4,5-trihydroxybenzoyl)oxy]oxan-2-yl]methyl 3,4,5-trihydroxybenzoate
  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：

  2-Deoxy-D-glucose 、 3,4,5-三苄氧基苯甲酸 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24.3%的产率得到2-deoxy-β-D-glucopyranose-1,3,4,6-tetrakis[3,4,5-tris(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

• 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.