3,8-dimethoxy-1-methylanthraquinone-2-carboxylic acid methyl ester | 945761-45-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 3,8-dimethoxy-1-methylanthraquinone-2-carboxylic acid methyl ester
• 英文别名: Methyl 3,8-dimethoxy-1-methyl-9,10-dioxoanthracene-2-carboxylate；methyl 3,8-dimethoxy-1-methyl-9,10-dioxoanthracene-2-carboxylate
• CAS: 945761-45-5
• 化学式: C₁₉H₁₆O₆
• 分子量: 340.332
• InChiKey: CRWVODHPRIMLFM-UHFFFAOYSA-N

物化性质

• 沸点：
  529.6±50.0 °C(Predicted)
• 密度：
  1.302±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  78.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,8-dimethoxy-1-methylanthraquinone-2-carboxylic acid methyl ester 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 作用下， 以 四氯化碳 为溶剂， 反应 24.0h， 以80%的产率得到methyl 1-(bromomethyl)-3,8-dimethoxy-9,10-dioxo-9,10-dihydroanthracene-2-carboxylate
  参考文献：
  名称：

  Structure–activity relationships of semisynthetic mumbaistatin analogs

  摘要：

  Mumbaistatin (1), a new anthraquinone natural product, is one of the most potent known inhibitors of hepatic glucose-6-phosphate translocase, an important target for the treatment of type II diabetes. Its availability, however, has been limited due to its extremely low yield from the natural source. Starting from DMAC (5, 3,8-dihydroxyanthraquinone-2-carboxylic acid), a structurally related polyketide product of engineered biosynthesis, we developed a facile semisynthetic method that afforded a variety of mumbaistatin analogs within five steps. This work was facilitated by the initial development of a DMAC overproduction system. In addition to reinforcing the biological significance of the anthraquinone moiety of mumbaistatin, several semisynthetic analogs were found to have low micromolar potency against the translocase in vitro. Two of them were also active in glucose release assays from primary hepatocytes. The synergistic combination of biosynthesis and synthesis is a promising avenue for the discovery of new bioactive substances. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.05.019
• 作为产物：
  描述：

  3,8-二羟基-1-甲基蒽醌-2-羧酸 、 碘甲烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3,8-dimethoxy-1-methylanthraquinone-2-carboxylic acid methyl ester 、 8-Hydroxy-3-methoxy-1-methylanthrachinon-2-carbonsaeure-methylester
  参考文献：
  名称：

  Structure–activity relationships of semisynthetic mumbaistatin analogs

  摘要：

  Mumbaistatin (1), a new anthraquinone natural product, is one of the most potent known inhibitors of hepatic glucose-6-phosphate translocase, an important target for the treatment of type II diabetes. Its availability, however, has been limited due to its extremely low yield from the natural source. Starting from DMAC (5, 3,8-dihydroxyanthraquinone-2-carboxylic acid), a structurally related polyketide product of engineered biosynthesis, we developed a facile semisynthetic method that afforded a variety of mumbaistatin analogs within five steps. This work was facilitated by the initial development of a DMAC overproduction system. In addition to reinforcing the biological significance of the anthraquinone moiety of mumbaistatin, several semisynthetic analogs were found to have low micromolar potency against the translocase in vitro. Two of them were also active in glucose release assays from primary hepatocytes. The synergistic combination of biosynthesis and synthesis is a promising avenue for the discovery of new bioactive substances. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.05.019

文献信息

• Structure–activity relationships of semisynthetic mumbaistatin analogs
  作者：Taek Soon Lee、Abhirup Das、Chaitan Khosla

  DOI：10.1016/j.bmc.2007.05.019

  日期：2007.8

  Mumbaistatin (1), a new anthraquinone natural product, is one of the most potent known inhibitors of hepatic glucose-6-phosphate translocase, an important target for the treatment of type II diabetes. Its availability, however, has been limited due to its extremely low yield from the natural source. Starting from DMAC (5, 3,8-dihydroxyanthraquinone-2-carboxylic acid), a structurally related polyketide product of engineered biosynthesis, we developed a facile semisynthetic method that afforded a variety of mumbaistatin analogs within five steps. This work was facilitated by the initial development of a DMAC overproduction system. In addition to reinforcing the biological significance of the anthraquinone moiety of mumbaistatin, several semisynthetic analogs were found to have low micromolar potency against the translocase in vitro. Two of them were also active in glucose release assays from primary hepatocytes. The synergistic combination of biosynthesis and synthesis is a promising avenue for the discovery of new bioactive substances. (c) 2007 Elsevier Ltd. All rights reserved.