2-hydroxy-7-methoxynaphthazarin | 3404-93-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-hydroxy-7-methoxynaphthazarin
• 英文别名: 2,5,8-trihydroxy-7-methoxy-1,4-naphthoquinone；mompain monomethyl ether；2,5,8-Trihydroxy-7-methoxy-1,4-naphthochinon；2-Hydroxy-7-methoxy-naphthazarin；7-Methoxy-2-hydroxy-naphthazarin
• CAS: 3404-93-1
• 化学式: C₁₁H₈O₆
• 分子量: 236.181
• InChiKey: VDXQPDMTTJQCEK-UHFFFAOYSA-N

物化性质

• 熔点：
  215-218 °C
• 沸点：
  600.5±55.0 °C(Predicted)
• 密度：
  1.706±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.93
• 重原子数：
  17.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  104.06
• 氢给体数：
  3.0
• 氢受体数：
  6.0

安全信息

• 海关编码：
  2914690090

反应信息

• 作为反应物：
  描述：

  2-hydroxy-7-methoxynaphthazarin 在 氢溴酸 、 盐酸甲胺 作用下， 以 乙醚 、 乙醇 、 叔丁醇 为溶剂， 反应 152.0h， 生成 6,8,9-trihydroxy-2,7-dimethyl-2-(4-methyl-3-pentenyl)-2H-naphtho<2,3-b>pyran-5,10-dione
  参考文献：
  名称：

  Chizhova, A. Ya.; Anufriev, V. F.; Novikov, V. L., Russian Journal of Organic Chemistry, 1995, vol. 31, # 2, p. 210 - 215

  摘要：

  DOI：
• 作为产物：
  描述：

  2-(1-bromoethyl)-5,8-dihydroxy-3,6-dimethoxy-1,4-naphthoquinone 在 水 、 sodium hydroxide 作用下， 反应 3.0h， 以22%的产率得到2-hydroxy-7-methoxynaphthazarin
  参考文献：
  名称：

  Synthesis of 2,2’-(ethane-l,l-diyl)bis(3,5,6,7,8-pentahydroxy-l,4-naphthoquinone), a metabolite of the sea urchins Spatangus purpureus, Strongylocentrotus intermedius, and S. droebachiensis

  摘要：

  合成 2,2'-(烷-l,l-二基)双(3,5,6,7,8-五羟基-l,4-萘醌)的一个关键步骤是在酸催化下，将 2-羟基萘酞与相应的醛缩合，醛是 2-羟基-3-(l-羟基烷基)萘酞的复醛反应产物。这种方法尤其适用于制备具有乙烷-1,1-二基桥的化合物，乙烷-1,1-二基桥是海胆 Spatangus purpureus、Strongylocentrotus intermedius 和 S. droebachiensis 产生的代谢物。

  DOI：

  10.1007/s11172-010-0265-2

文献信息

• Spinochrome synthesis
  作者：I. Singh、R.E. Moore、C.W.J. Chang、R.T. Ogata、P.J. Scheuer

  DOI：10.1016/s0040-4020(01)98704-6

  日期：1968.1

  widely distributed structural pigments of the sea urchins (echinoids) one (spinochrome B) is a derivative of juglone, while four (spinochromes A, C, D, and E) are derivatives of naphthazarin. In addition to the two peri OH groups of naphthazarin these compounds bear one or more β-hydroxyls and/or an acetyl side chain. The synthesis of these four naphthazarin derivatives is described. The naphthalene skeleton

  在海胆的五种广泛分布的结构性颜料（类神经碱）中，一种（螺闪体色素B）是朱古龙的衍生物，而四种（螺闪体色素A，C，D和E）是萘甲萘林的衍生物。除了这两个围萘他沙林的OH基团带有一个或多个β-羟基和/或乙酰基侧链。描述了这四种萘他林衍生物的合成。萘骨架是通过将1,2-二羟基-3,4-二甲氧基苯与氯-或二氯马来酸酐在铝-氯化钠熔体中缩合而构建的。通过用甲醇盐离子的亲核取代氯或通过Thiele方法引入了更多的氧官能团。通过制备无色乙酸酯并将其用乙酸酐-三氟化硼处理，将乙酰基侧链连接至聚羟基萘醌。在加工过程中水解和氧化后，萘扎林体系得以再生。
• Synthesis, Cytotoxic Activity Evaluation and Quantitative Structure-ActivityAnalysis of Substituted 5,8-Dihydroxy-1,4-naphthoquinones and Their O- and S-Glycoside Derivatives Tested against Neuro-2a Cancer Cells
  作者：Sergey Polonik、Galina Likhatskaya、Yuri Sabutski、Dmitry Pelageev、Vladimir Denisenko、Evgeny Pislyagin、Ekaterina Chingizova、Ekaterina Menchinskaya、Dmitry Aminin

  DOI：10.3390/md18120602

  日期：——

  increase in the cytotoxic activity of acetylated thioglycosidesof NQs, which was partially retained for their deacetylated derivatives. Thiomethylglycosides of 2-hydroxy-1,4-NQs with OH and MeO groups in quinone core at positions 6 and 7, resprectively formed a nontoxic set of compounds with EC50 > 100 μM. A quantitative structure-activity relationship (QSAR) model of cytotoxic activity of 22 1,4-NQ derivatives

  基于源自海胆的6,7-取代的2,5,8-三羟基-1,4-萘醌（1,4-NQs），制备了五种新的NQs乙酰-O-葡萄糖苷。开发了一种通过亚甲基间隔基将过O-乙酰化的1-巯基糖与2-羟基-1,4-NQ偶联的新方法。重氮甲烷使乙酰硫基甲基糖苷的醌核心的2-羟基甲基化和糖部分的脱乙酰基导致28个新的2-羟基-和2-甲氧基-1,4-NQs的硫代甲基糖苷。通过MTT方法测定了起始的1，4-NQs（13种化合物）及其O-和S-糖苷衍生物（37种化合物）对Neuro-2a小鼠神经母细胞瘤细胞的细胞毒活性。具有EC 50的细胞毒性化合物= 2.7–87.0μM ，发现EC 50 > 100μM的无毒化合物。乙酰化的O-和S-糖苷1,4-NQ最有效，EC 50 = 2.7-16.4μM。2-OH基萘醌核心的甲基化导致NQs的乙酰化硫糖苷的细胞毒活性急剧增加，而NQs的乙酰化硫糖苷部分保留了它们的脱乙酰基衍生物。2-羟基-1
• Activity of New Synthetic (2-Chloroethylthio)-1,4-naphthoquinones in Prostate Cancer Cells
  作者：Sergey A. Dyshlovoy、Dmitry N. Pelageev、Lea S. Jakob、Ksenia L. Borisova、Jessica Hauschild、Tobias Busenbender、Moritz Kaune、Ekaterina A. Khmelevskaya、Markus Graefen、Carsten Bokemeyer、Victor Ph. Anufriev、Gunhild von Amsberg

  DOI：10.3390/ph14100949

  日期：——

  Development of resistance to currently available standard therapies in advanced prostate cancer (PCa) emphasizes the need for novel therapeutic options. Here, we report the synthesis of new hybrid molecules consisting of 2-chloroethylthio and 1,4-naphthoquinone pharmacophores and describe their activity in PCa. In screening analyses, the introduction of one 2-chloroethylthio group improved the anticancer properties of 1,4-naphthoquinones, whereas the introduction of a second 2-chloroethylthio moiety rather decreased activity. Two most promising of the synthesized compounds, 30 and 32, were highly active in different human PCa cell lines harboring varying resistance profiles at nanomolar concentrations. The generated data suggest that the compounds are capable of mitochondria targeting, cytotoxic ROS induction, and DNA damage, which resulted in apoptosis presumably executed in a caspase-dependent manner. The substances synergized with the clinically approved PARP inhibitor olaparib and resensitized AR-V7-expressing PCa cells to antiandrogen enzalutamide, as well as to a combination of enzalutamide and an AKT inhibitor. This was at least in part exerted via down-regulation of AR-V7 expression and inhibition of AR signaling. Mild antagonism was observed in combination with platinum- or taxane-based chemotherapy, which was putatively related to treatment-induced activation of p38, JNK1/2, ERK1/2, MEK1/2, and AKT, functioning as potential pro-survival factors. Thus, the synthesized (2-chloroethylthio)-1,4-naphthoquinone derivatives exhibit promising anticancer properties in vitro, suggesting their further development as potential therapeutics for the treatment of castration-resistant PCa.

  目前，晚期前列腺癌（PCa）对现有标准疗法的耐药性的发展强调了新型治疗选择的必要性。在这里，我们报道了2-氯乙基硫和1,4-萘醌药效团组成的新型杂化分子的合成，并描述了它们在PCa中的活性。在筛选分析中，引入一个2-氯乙基硫基团改善了1,4-萘醌的抗癌性能，而引入第二个2-氯乙基硫基团则降低了活性。合成的两个最有前途的化合物30和32，在不同人类PCa细胞系中具有高活性，这些细胞系具有不同的耐药谱，浓度为纳摩尔级。生成的数据表明，这些化合物能够靶向线粒体，诱导细胞毒性ROS和DNA损伤，导致凋亡，可能是以caspase依赖的方式执行的。这些物质与临床批准的PARP抑制剂olaparib协同作用，并使表达AR-V7的PCa细胞重新对抗雄激素受体拮抗剂恩扎鲁胺以及恩扎鲁胺和AKT抑制剂的联合治疗产生敏感性。这至少部分是通过下调AR-V7表达和抑制AR信号传导来发挥作用的。与铂类或紫杉醇类化疗的联合治疗中观察到轻度的拮抗作用，这可能与治疗引起的p38、JNK1/2、ERK1/2、MEK1/2和AKT的潜在促生存因子的活化有关。因此，合成的（2-氯乙基硫基）-1,4-萘醌衍生物在体外展示了有前途的抗癌性能，建议将其进一步开发为治疗去势抵抗性PCa的潜在治疗药物。
• Polycyclic hydroxyquinones—VIII
  作者：Francisco Farin˜a、Roberto Martinez-Utrilla、M. Carmen Paredes

  DOI：10.1016/0040-4020(82)80244-5

  日期：1982.1

  Several synthetic routes to mono- and dihydroxynaphthazarins bearing an acetyl side-chain have been explored. Methoxynaphthazarin1 has always been the starting material. Acylation is brought aboutvia a photo-Fries rearrangement of various adequately substituted acetoxynaphthalenes prepared in several steps from1. Further steps including oxidative demethylation, hydrolysis and ether cleavage reactions

  已探索了几种带有乙酰基侧链的单和二羟基萘达那林的合成途径。甲氧基萘他林1一直是起始原料。通过从1开始的多个步骤制备的各种适当取代的乙酰氧基萘的光-弗里斯重排，实现酰化作用。进一步的步骤，包括氧化脱甲基，水解和醚裂解反应，产生了所需的单和二羟基取代的乙酰萘。描述了新合成的Spinochrome A 24（一种代表这种萘达那林衍生物的天然色素）。
• A Simple Route to Benzo[b]xanthene-6,11,12-triones: Synthesis of Bikaverin
  作者：Victor Anufriev、Dmitry Pelageev、Ksenia Borisova

  DOI：10.1055/s-0036-1591587

  日期：2018.10

  Fusarium, and Mycogone, was synthesised. A three-step procedure for the synthesis of 1H-benzo[b]xanthene-6,11,12-trione derivatives is described. The procedure involves the halogenation of 12-(3-hydroxy-1,4-naphthoquinon-2-yl)-6H-benzo[b]xanthene-6,11-(12H)-diones, followed by treatment with water under aeration. In this manner, bikaverin, a cytotoxic metabolite isolated from several species of the fungal

  摘要 描述了合成1 H-苯并[ b ]氧杂蒽-6,11,12-三酮衍生物的三步程序。该程序包括将12-（3-羟基-1,4-萘醌-2-基）-6 H-苯并[ b ]]吨-6,11-（12 H）-二酮卤化，然后在减压下用水处理通风。以这种方式，合成了比卡韦林，这是一种从真菌属赤霉菌，镰刀菌属和霉菌酮的几种物种中分离出来的细胞毒性代谢产物。 描述了合成1 H-苯并[ b ]氧杂蒽-6,11,12-三酮衍生物的三步程序。该程序包括将12-（3-羟基-1,4-萘醌-2-基）-6 H-苯并[ b ]]吨-6,11-（12 H）-二酮卤化，然后在减压下用水处理通风。以这种方式，合成了比卡韦林，这是一种从真菌属赤霉菌，镰刀菌属和霉菌酮的几种物种中分离出来的细胞毒性代谢产物。