(S)-1-(1, 4-dimethoxy-5,8-dioxo-5,8-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl acetate | 959120-52-6

• 分子结构分类: 有机化合物
• 英文名称: (S)-1-(1, 4-dimethoxy-5,8-dioxo-5,8-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl acetate
• 英文别名: (S)-1-(1,4-dimethoxy-5,8-dioxo-5,8-dihydronaphthalen-2-yl)-4-methylpent-3-enyl acetate
• CAS: 959120-52-6
• 化学式: C₂₀H₂₂O₆
• 分子量: 358.391
• InChiKey: WLEJFGDOMNFULT-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  78.9
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (S)-1-(1, 4-dimethoxy-5,8-dioxo-5,8-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl acetate 在 吡啶 、 盐酸羟胺 作用下， 以 乙醇 为溶剂， 生成 (S)-1-((5E,8E)-5,8-bis(hydroxyimino)-1,4-dimethoxy-5,8-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl acetate
  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：

  (S)-4-methyl-1-(1,4,5,8-tetramethoxynaphthalen-2-yl)pent-3-en-1-yl acetate 在 ammonium cerium (IV) nitrate 作用下， 以 水 为溶剂， 反应 0.25h， 生成 (S)-1-(1, 4-dimethoxy-5,8-dioxo-5,8-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl acetate
  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

文献信息

• 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。
• An Efficient Multigram Synthesis of Alkannin and Shikonin
  作者：Rubing Wang、Shanshan Zhou、Hudagula Jiang、Xiaogang Zheng、Wen Zhou、Shaoshun Li

  DOI：10.1002/ejoc.201101505

  日期：2012.3

  The concise and efficient total syntheses of alkannin (1) and shikonin (2), based on the resolution of a key acid intermediate, are achieved with excellent enantiomeric excesses and high overall yields (99 % ee, 15.6 % for 1 and 99.8 % ee, 11.9 % for 2). The key steps of the synthetic strategy involve the convenient synthesis and separation of a pair of amide diastereoisomers and the mild hydrolysis

  基于对关键酸中间体的拆分，实现了链烷酸 (1) 和紫草素 (2) 简洁高效的全合成，具有优异的对映体过量和高总产率（99 % ee，15.6 % 1 和 99.8 % ee , 11.9 % 为 2)。该合成策略的关键步骤包括一对酰胺非对映异构体的方便合成和分离以及酰胺的温和水解以去除胺手性助剂，以及甲基保护基团的有效脱保护序列。