(R)-2-(1-hydroxy-4-methylpent-3-enyl)-5,8-dimethoxynaphthalene-1,4-dione

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (R)-2-(1-hydroxy-4-methylpent-3-enyl)-5,8-dimethoxynaphthalene-1,4-dione
• 英文别名: 2-(1-hydroxy-4-methylpent-3-en-1-yl)-5,8-dimethoxynaphthalene-1,4-dione；5,8-O-dimethylshikonin；2-(1-hydroxy-4-methylpent-3-enyl)-5,8-dimethoxynaphthalene-1,4-dione；2-[(1R)-1-hydroxy-4-methylpent-3-enyl]-5,8-dimethoxynaphthalene-1,4-dione
• 化学式: C₁₈H₂₀O₅
• 分子量: 316.354
• InChiKey: GXKBSCZWXXVZIU-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  β-羟基异戊酸 、 (R)-2-(1-hydroxy-4-methylpent-3-enyl)-5,8-dimethoxynaphthalene-1,4-dione 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， 以37.1%的产率得到(R)-1-(5,8-dimethoxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl 3-hydroxy-3-methylbutanoate
  参考文献：
  名称：

  Semi-synthesis and anti-tumor activity of 5,8-O-dimethyl acylshikonin derivatives

  摘要：

  A set of twenty-two 5,8-O-dimethyl acylshikonin derivatives were designed and synthesized starting from shikonin. The cell-based investigation demonstrated that these dimethylated derivatives were less active than or equally effective to shikonin. However, the selective cytotoxicities toward MCF-7 were found among these derivatives, together with no toxicity in the normal cell. Furthermore, compounds 3f, 3p, 3r were subjected to Km mice suffering from S-180 carcinoma subcutaneously, which possessed more potent than Fluorouracil, a typical anticancer drug used clinically. So we may conclude that the modification to the mother nucleus of shikonin via the methylation is an available approach to acquiring anti-tumor agents with higher selectivity and lower toxicity. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.09.068
• 作为产物：
  描述：

  4-甲基-3-戊烯酸 在 吡啶 、 正丁基锂 、 硼烷四氢呋喃络合物 、 四溴化碳 、 (R)-Corey oxazaborolidine 、 三苯基膦 、 叔丁醇 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 10.66h， 生成 (R)-2-(1-hydroxy-4-methylpent-3-enyl)-5,8-dimethoxynaphthalene-1,4-dione
  参考文献：
  名称：

  A New Efficient Route for Multigram Asymmetric Synthesis of Alkannin and Shikonin

  摘要：

  A short and convergent approach for the synthesis of alkannin, shikonin and shikalkin is presented. A Hauser-type annulation of cyanophthalide 26 with enone 7 affords the complete aromatic system in just one step with concomitant attachment of the entire side chain. Subsequent Corey's oxazaborolidine mediated asymmetric reduction of the above advanced intermediate, leads to the required isomer in high enantiomeric excess. Finally, a selective and high yielding deprotection protocol furnishes the title compounds as pure crystalline precipitates. Thus, a multigram synthesis of shikonin, alkannin and shikalkin is achieved in high yield and enantioselectivity.

  DOI：

  10.1002/1521-3765(20020415)8:8<1795::aid-chem1795>3.0.co;2-v

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。
• Design, synthesis and anticancer activity of naphthoquinone derivatives
  作者：Xiao-bao Shen、Yang Wang、Xuan-zhen Han、Liang-quan Sheng、Fu-fang Wu、Xinhua Liu

  DOI：10.1080/14756366.2020.1740693

  日期：2020.1.1

  were designed and synthesised. With the help of reverse targets searching, anti-cancer activity was preliminarily evaluated, most of them are effective against some tumour cells, especially compound 12: 1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl-4-oxo-4-((4-phenoxyphenyl)amino) butanoate whose IC50 against SGC-7901 was 4.1 ± 2.6 μM. Meanwhile the anticancer mechanism

  摘要 基于萘醌部分的分子对接和药效团分析，总共设计和合成了23种化合物。借助反向靶标搜索，初步评估了其抗癌活性，其中大多数对某些肿瘤细胞有效，尤其是化合物12：1-（5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen -2-基）-4-甲基戊-3-烯-1-基-4-氧代-4-（（4-苯氧基苯基）氨基）丁酸酯，其对SGC-7901的IC 50为4.1±2.6μM。同时通过AnnexinV / PI染色，免疫荧光，Western印迹分析和分子对接研究了化合物12的抗癌机理。结果表明该化合物可能通过调节PI3K信号通路诱导细胞凋亡和细胞自噬。
• A Partial Synthesis of 5,8-O-Dimethylshikonin and 6-Isomer of 5,8-O-Dimethylshikonin
  作者：Xiaogang Zheng、Rubing Wang、Mengyuan Zhu、Zheng Jing、Shaoshun Li

  DOI：10.3184/174751911x13202594578071

  日期：2011.11

  milder and more environmentally friendly to environment, avoiding the use of the toxic and expensive reagents methyl iodide and chloromethyl ether and are more applicable to large-scale preparation. This is important because shikonin and its closely related derivatives have attracted much attention in view of their antitumor activities.

  5, 8-O-二甲基紫草素和 5,8-O-二甲基紫草素的 6-异构体的方便合成以 81.8% 的总产率从紫草素中得到发展。(R)-4-Methyl-1-(1,4,5,8-tetramethoxynaphthalen-2-yl)pent-3-en-1-ol 以一锅两步法制备，然后用高铈氧化硝酸铵。这更简单，并且总产率高于以前的方法。反应条件更温和，更环保，避免使用有毒、昂贵的碘甲烷和氯甲醚试剂，更适合大规模制备。这很重要，因为紫草素及其密切相关的衍生物因其抗肿瘤活性而备受关注。
• [EN] SHIKONIN NAPHTHAZARIN DERIVATIVES, PREPARATION METHOD AND ANTITUMOR USE THEREOF<br/>[FR] DÉRIVÉS DE SHIKONINE NAPHTAZARINE, LEUR PROCÉDÉ DE PRÉPARATION ET UTILISATION ANTITUMORALE
  申请人：UNIV SHANGHAI JIAOTONG

  公开号：WO2011113284A1

  公开（公告）日：2011-09-22

  Shikonin naphthazarin derivatives represented by formula I and their preparation method are disclosed, wherein Ri~R4 and R are defined as in the description. The antitumor use of the compounds is also disclosed.
• Semi-synthesis and anti-tumor activity of 5,8-O-dimethyl acylshikonin derivatives
  作者：Wen Zhou、Ying Peng、Shao-Shun Li

  DOI：10.1016/j.ejmech.2010.09.068

  日期：2010.12

  A set of twenty-two 5,8-O-dimethyl acylshikonin derivatives were designed and synthesized starting from shikonin. The cell-based investigation demonstrated that these dimethylated derivatives were less active than or equally effective to shikonin. However, the selective cytotoxicities toward MCF-7 were found among these derivatives, together with no toxicity in the normal cell. Furthermore, compounds 3f, 3p, 3r were subjected to Km mice suffering from S-180 carcinoma subcutaneously, which possessed more potent than Fluorouracil, a typical anticancer drug used clinically. So we may conclude that the modification to the mother nucleus of shikonin via the methylation is an available approach to acquiring anti-tumor agents with higher selectivity and lower toxicity. (C) 2010 Elsevier Masson SAS. All rights reserved.