2,5-dimethylpyrano[2,3,4-ij]isoquinolin-8-ol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 2,5-dimethylpyrano[2,3,4-ij]isoquinolin-8-ol
• 英文别名: cassarian A；cassiarin A
• 化学式: C₁₃H₁₁NO₂
• 分子量: 213.236
• InChiKey: PEFIRMBVFBVVGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.0
• 重原子数：
  16.0
• 可旋转键数：
  0.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  42.35
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2,5-dimethylpyrano[2,3,4-ij]isoquinolin-8-ol 、 2-氯乙醇 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 48.5h， 生成 2-[(3,7-Dimethyl-2-oxa-6-azatricyclo[7.3.1.05,13]trideca-1(13),3,5,7,9,11-hexaen-11-yl)oxy]ethanol
  参考文献：
  名称：

  Synthesis, cytotoxicity, DNA binding and topoisomerase II inhibition of cassiarin A derivatives

  摘要：

  Four series of cassiarin A derivatives with alkanoyl (3a-3d), aroyl (4a-4d), hydroxy/amino-substituted ethylene glycol (5a-5c) and selenium-containing (6a) side chains were synthesized. Their antitumor activities were evaluated against BT474, CHAGO, HepG2, KATO-III, SW620 and CaSki cancer cell lines. Preliminary results demonstrated that 5b had moderate activities against HepG2 and KATO-III cell lines, while 5c showed moderate to high cytotoxicity against most tested cell lines. In addition, 6a exhibited moderate cytotoxicity against cervical cells, CaSki. DNA-binding and ethidium bromide displacement experiments suggested that 5c and 5b binds to DNA via an intercalative mode, whereas 6a did not. However, the selenium-containing cassiarin A derivative 6a inhibited topoisomerase II with more than 95% inhibition at the concentration of 50 mu M. These cassiarin A derivatives showed lower toxicity to normal cells, WI-38 than amonafide therefore they are potential lead compounds to be further developed as new anticancer agents. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.107
• 作为产物：
  描述：

  羟基甲基氧丙基苯并吡喃酮 在 ammonium acetate 、 溶剂黄146 作用下， 反应 48.0h， 以91%的产率得到2,5-dimethylpyrano[2,3,4-ij]isoquinolin-8-ol
  参考文献：
  名称：

  决明子A作为潜在抗疟疾药物具有血管舒张活性的合成及其构效关系

  摘要：

  从决明子（Lesiaminosae）的叶子中分离出的三环生物碱Cassiarin A 1对恶性疟原虫和体内的伯氏疟原虫具有强大的抗疟疾活性，这可能是新型抗疟疾的有价值的线索。在导致严重疟疾发病机理的过程中，被寄生的红细胞（pRBC）与主动脉内皮的相互作用尤为重要。一氧化氮（NO）减少了pRBC粘附于血管内皮的受体/粘附分子的内皮表达，并降低了pRBC对血管内皮的细胞粘附。决明A 1表现出对大鼠主动脉环的血管舒张活性，这可能与一氧化氮的产生有关。一系列的羟基和氮取代的衍生物和的脱衍生物的1已被合成为具有针对有效的抗疟药恶性疟原虫具有血管舒张活性，这可以减少的pRBC的细胞粘连至血管内皮。决明子A 1在体外表现出有效的抗疟疾活性和高选择性指数，表明没有任何取代基的羟基和氮原子的存在对于显示抗疟疾活性可能很重要。相对于决明子A，甲氧基衍生物显示出更强的血管舒张活性，尽管它并未显示出对恶性疟原虫抑

  DOI：

  10.1016/j.bmc.2009.10.013

文献信息

• Pd(II)-Catalyzed Annulation Reactions of Epoxides with Benzamides to Synthesize Isoquinolones
  作者：Huihong Wang、Fei Cao、Weiwei Gao、Xiaodong Wang、Yuhang Yang、Tao Shi、Zhen Wang

  DOI：10.1021/acs.orglett.0c04097

  日期：2021.2.5

  Epoxides as alkylating reagents are unprecedentedly applied in Pd(II)-catalyzed C–H alkylation and oxidative annulation of substituted benzamides to synthesize isoquinolones rather than isochromans, which is accomplished through alerting the previously reported reaction mechanism by the addition of oxidant and TEA. Under these conditions, various isoquinolones have been prepared with yields up to 92%

  环氧化合物作为烷基化试剂已史无前例地应用于Pd（II）催化的CH烷基化和取代的苯甲酰胺的氧化环化反应，以合成异喹诺酮而不是异色满，这是通过提醒氧化剂和TEA来警告先前报道的反应机理而实现的。在这些条件下，已制备了各种异喹诺酮，收率高达92％。另外，该方法已经以一种方便的方式成功地用于了卢比西替利，siamine和cassiarin A的全部合成中。
• Biomimetic Total Syntheses of Cassiarins A and B
  作者：Yuan-Shan Yao、Zhu-Jun Yao

  DOI：10.1021/jo801017b

  日期：2008.7.1

  Total syntheses of cassiarins A and B have been efficiently accomplished using a common strategy with biomimetic considerations. Key reactions involved in this synthesis include a Negishi-type coupling, a Ag(I)-promoted formation of the tricyclic 8H-pyrano[2,3,4-de]chromen-8-one core, and a sequential amine-condensation and cyclization. Three new analogues of cassiarin A bearing different substituents

  使用仿生学的通用策略已有效地完成了卡西林A和B的总合成。参与该合成的关键反应包括Negishi型偶联，Ag（I）促进的三环8 H-吡喃并[2,3,4- de ] chromen -8-one核的形成以及顺序的胺缩合和环化。从同一中间体平行合成了三个新的肉桂素A类似物，它们在C-11位置带有不同的取代基。另外，从相应的化学等效前体获得了对关键三环核心和卡西林A和B的另外两个转化。
• Synthesis of 1-Substituted Isoquinolines by Heterocyclization of TosMIC Derivatives: Total Synthesis of Cassiarin A
  作者：Sara Gutiérrez、Anna Coppola、David Sucunza、Carolina Burgos、Juan J. Vaquero

  DOI：10.1021/acs.orglett.6b01521

  日期：2016.7.15

  A new method for the synthesis of 1-substituted isoquinolines by a heterocyclization that involves α-benzyl TosMIC derivatives and different electrophiles has been developed. This methodology has been successfully applied to a total synthesis of cassiarin A, an alkaloid with potent antiplasmodial activity against Plasmodium falciparum.

  通过涉及α-苄基TosMIC衍生物和不同亲电试剂的杂环化合成1-取代异喹啉的新方法已经被开发出来。该方法已成功地应用于决明子A的全合成，这是一种对恶性疟原虫具有有效抗疟原虫活性的生物碱。
• First Total Synthesis of Cassiarin A, a Naturally Occurring Potent Antiplasmodial Alkaloid
  作者：Marcellino Rudyanto、Yuichiro Tomizawa、Hiroshi Morita、Toshio Honda

  DOI：10.1021/ol8004112

  日期：2008.5.1

  The first total synthesis of cassiarin A, an antiplasmodial alkaloid isolated from Cassia siamea, was achieved via sequential alkynylation of arenes with Sonogashira coupling and 6- endo-dig-cyclization of phenolic oxygens to the resulting alkynes.

  决明子A（一种从决明子中分离得到的抗疟原虫生物碱）的第一个全合成是通过将芳烃与Sonogashira偶联依次进行炔基烷基化和酚内氧的6-内切-环化反应生成的炔烃而实现的。
• Chrobisiamone A, a new bischromone from Cassia siamea and a biomimetic transformation of 5-acetonyl-7-hydroxy-2-methylchromone into cassiarin A
  作者：Shiori Oshimi、Yuichiro Tomizawa、Yusuke Hirasawa、Toshio Honda、Wiwied Ekasari、Aty Widyawaruyanti、Marcellino Rudyanto、Gunawan Indrayanto、Noor Cholies Zaini、Hiroshi Morita

  DOI：10.1016/j.bmcl.2008.05.041

  日期：2008.7

  A new bischromone, chrobisiamone A (1) with an antiplasmodial activity has been isolated from the leaves of Cassia siamea and the structure was elucidated by 2D NMR analysis. Cyclization of 5-acetonyl-7-hydroxy-2-methylchromone (2) in the presence of ammonium acetate resulted in generation of cassiarin A (3) with an unprecedented tricyclic skeleton, supporting a biogenetic pathway proposed for 3.

  从决明子的叶片中分离出了一种具有抗疟原虫活性的新双色酮，Chrobisiamone A（1），并通过2D NMR分析阐明了其结构。在乙酸铵存在下将5-丙酮基-7-羟基-2-甲基色酮（2）环化导致生成具有空前三环骨架的决明子A（3），支持为3提出的生物遗传途径。