(R)-1-(1,4-dimethoxy-5,8-dioxo-5,8-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl 3-hydroxy-3-methylbutanoate | 1016167-34-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (R)-1-(1,4-dimethoxy-5,8-dioxo-5,8-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl 3-hydroxy-3-methylbutanoate
• 英文别名: [(1R)-1-(1,4-dimethoxy-5,8-dioxonaphthalen-2-yl)-4-methylpent-3-enyl] 3-hydroxy-3-methylbutanoate
• CAS: 1016167-34-2
• 化学式: C₂₃H₂₈O₇
• 分子量: 416.471
• InChiKey: OBWIRPONJUSPCC-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  99.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-1-(1,4-dimethoxy-5,8-dioxo-5,8-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl 3-hydroxy-3-methylbutanoate 在 吡啶 、 盐酸羟胺 作用下， 以 乙醇 为溶剂， 生成 (R)-1-((5E,8E)-5,8-bis(hydroxyimino)-1,4-dimethoxy-5,8-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl 3-hydroxy-3-methylbutanoate
  参考文献：
  名称：

  Synthesis and evaluation of novel alkannin and shikonin oxime derivatives as potent antitumor agents

  摘要：

  A set of forty alkannin and shikonin oxime derivatives were firstly designed and synthesized. Their cytotoxicities against three kinds of tumor cells and a normal cell line were tested and compared with alkannin and shikonin. The cell-based investigation demonstrated that some oxime derivatives were more or comparatively effective to the lead compounds, especially their selective and excellent antitumor activities towards K562 cells with no toxicity in normal cells. We may conclude that oximate modification to the mother nucleus of alkannin and shikonin is an available approach to acquire potent antitumor agents.

  DOI：

  10.1016/j.bmcl.2014.07.012
• 作为产物：
  描述：

  β-羟基异戊酸 在 4-二甲氨基吡啶 、 ammonium cerium (IV) nitrate 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 0.25h， 生成 (R)-1-(1,4-dimethoxy-5,8-dioxo-5,8-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl 3-hydroxy-3-methylbutanoate
  参考文献：
  名称：

  紫草宁和烷烃衍生物作为潜在抗癌药的设计，合成和生物评价，通过前药方法

  摘要：

  为了最大程度地减少由于活性氧（ROS）的生成和萘达沙林环烷基化而产生的紫草素和链烷素的细胞毒性，设计了两个系列的新型核心骨架修饰的紫草素和链烷素衍生物。这些衍生物的构型和位置异构性不同（R-，S-，2-和6-异构体）以高对映体过量（> 99％ee）合成 ）。在体外，二甲基化衍生物的选择性显着高于母体紫草素，但在体内仍观察到一些副作用。令人惊讶的是，体外抗癌活性较差的二甲基化二乙酰基衍生物显示出与紫杉醇相似的肿瘤抑制作用，而在体内却没有任何毒性。这些衍生物的抗癌活性与其低ROS生成和烷基化能力相符，强调了其作为前药的潜力。该策略提供了解决萘他林类似物对正常细胞的非特异性细胞毒性的手段。

  DOI：

  10.1002/cmdc.201402224

文献信息

• Synthesis and evaluation of novel alkannin and shikonin oxime derivatives as potent antitumor agents
  作者：Rubing Wang、Xu Zhang、Hualong Song、Shanshan Zhou、Shaoshun Li

  DOI：10.1016/j.bmcl.2014.07.012

  日期：2014.9

  A set of forty alkannin and shikonin oxime derivatives were firstly designed and synthesized. Their cytotoxicities against three kinds of tumor cells and a normal cell line were tested and compared with alkannin and shikonin. The cell-based investigation demonstrated that some oxime derivatives were more or comparatively effective to the lead compounds, especially their selective and excellent antitumor activities towards K562 cells with no toxicity in normal cells. We may conclude that oximate modification to the mother nucleus of alkannin and shikonin is an available approach to acquire potent antitumor agents.
• Design, Synthesis, and Biological Evaluation of Shikonin and Alkannin Derivatives as Potential Anticancer Agents via a Prodrug Approach
  作者：Ru-Bing Wang、Wen Zhou、Qing-Qing Meng、Xu Zhang、Jing Ding、Yan Xu、Hua-Long Song、Kai Yang、Jia-Hua Cui、Shao-Shun Li

  DOI：10.1002/cmdc.201402224

  日期：2014.12

  observed in vivo. Surprisingly, the dimethylated diacetyl derivatives with poor anticancer activity in vitro showed tumor‐inhibiting effects similar to paclitaxel without any toxicity in vivo. The anticancer activity of these derivatives is in agreement with their low ROS generation and alkylating capacity, emphasizing their potential as prodrugs. This strategy provides means to address the nonspecific

  为了最大程度地减少由于活性氧（ROS）的生成和萘达沙林环烷基化而产生的紫草素和链烷素的细胞毒性，设计了两个系列的新型核心骨架修饰的紫草素和链烷素衍生物。这些衍生物的构型和位置异构性不同（R-，S-，2-和6-异构体）以高对映体过量（> 99％ee）合成 ）。在体外，二甲基化衍生物的选择性显着高于母体紫草素，但在体内仍观察到一些副作用。令人惊讶的是，体外抗癌活性较差的二甲基化二乙酰基衍生物显示出与紫杉醇相似的肿瘤抑制作用，而在体内却没有任何毒性。这些衍生物的抗癌活性与其低ROS生成和烷基化能力相符，强调了其作为前药的潜力。该策略提供了解决萘他林类似物对正常细胞的非特异性细胞毒性的手段。