(+)-(R,E)-6-acetyl-2-(1-(2-(diethyl)amino)ethylidene)-7,9-dihydroxy-8,9b-dimethyldibenzo[b,d]furan-1,3(2H,9bH)-dione | 1414940-98-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (+)-(R,E)-6-acetyl-2-(1-(2-(diethyl)amino)ethylidene)-7,9-dihydroxy-8,9b-dimethyldibenzo[b,d]furan-1,3(2H,9bH)-dione
• 英文别名: (2R,4E)-10-acetyl-4-(1-{[2-(diethylamino)ethyl]amino}ethylidene)-11,13-dihydroxy-2,12-dimethyl-8-oxatricyclo[7.4.0.0^2,7]trideca-1(9),6,10,12-tetraene-3,5-dione；(E)-6-acetyl-2-(1-((2-(diethylamino)ethyl)amino)ethylidene)-7,9-dihydroxy-8,9b-dimethyldibenzo[b,d]furan-1,3-(2H,9bH)-dione；(2E,9bR)-6-acetyl-2-[1-[2-(diethylamino)ethylamino]ethylidene]-7,9-dihydroxy-8,9b-dimethyldibenzofuran-1,3-dione
• CAS: 1414940-98-9
• 化学式: C₂₄H₃₀N₂O₆
• 分子量: 442.512
• InChiKey: XTFRZXAXMLVDQI-VRBZIXIWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  116
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (+)-(R,E)-6-acetyl-2-(1-(2-(diethyl)amino)ethylidene)-7,9-dihydroxy-8,9b-dimethyldibenzo[b,d]furan-1,3(2H,9bH)-dione 、 碘甲烷 以 二氯甲烷 为溶剂， 反应 72.0h， 以88%的产率得到(2R,4E)-10-acetyl-4-[1-({2-[diethyl(methyl)amino]ethyl}amino)ethylidene]-11,13-dihydroxy-2,12-dimethyl-8-oxatricyclo[7.4.0.0^2,7]trideca-1(9),6,10,12-tetraene-3,5-dione iodide
  参考文献：
  名称：

  Synthesis and Biological Activity of Usnic Acid Enamine Derivatives

  摘要：

  松萝酸的两个对映体及其与季铵化N原子的相应化合物的衍生物被合成。化合物3和4表现出中等的细胞毒活性。所有季铵化化合物对测试的肿瘤细胞系均无活性。季铵化化合物7和8对用于抗结核药物筛选的主要测试物种——耻垢分枝杆菌显示出高抗分枝杆菌活性。结果表明，活性与N原子之间连接链长度的增加呈下降趋势。化合物（+）-8有效地抑制了病原性革兰氏阳性微生物金黄色葡萄球菌、表皮葡萄球菌、肺炎链球菌和粪肠球菌的生长。

  DOI：

  10.1007/s10600-015-1376-7
• 作为产物：
  描述：

  (+)-usnic acid 、 N,N-二乙基乙二胺 以 乙醇 为溶剂， 反应 3.0h， 以88%的产率得到(+)-(R,E)-6-acetyl-2-(1-(2-(diethyl)amino)ethylidene)-7,9-dihydroxy-8,9b-dimethyldibenzo[b,d]furan-1,3(2H,9bH)-dione
  参考文献：
  名称：

  （-）-和（+）-松香酸及其衍生物对流感病毒A（H1N1）2009的抗病毒活性

  摘要：

  流感是一种广泛的呼吸道感染。每年，它引起流行病，迅速在一个国家到另一个国家传播，甚至流行，涉及地球上很大一部分人口。作为高度可变的感染，流感很容易累积对许多抗病毒药的耐药性突变。 松香酸是一种最初从地衣中分离出来的二苯并呋喃，属于次生代谢产物，具有广泛的生物活性。在人类中，它可以充当消炎药，抗有丝分裂药，抗肿瘤药，抗菌药和抗真菌药。在这项工作中，我们首次研究了松萝酸及其衍生物对大流行性流感病毒A（H1N1）pdm09的抗病毒活性。分别通过微四唑鎓试验和病毒产量试验分别测试了代表松萝酸的（+）和（-）异构体的26种化合物及其衍生物在MDCK细胞中的细胞毒性和抗病毒活性。根据获得的结果，细胞毒性剂量（CTD 50）为50％，有效剂量为50％（ED 50））和每种化合物的选择性指数（SI）。发现其中11个的SI高于10（最高值为37.3）。已证明绝对构型对抗病毒活性具有至关重要的意义。除少数例外

  DOI：

  10.1016/j.bmcl.2012.09.084

文献信息

• Anti-viral activity of (−)- and (+)-usnic acids and their derivatives against influenza virus A(H1N1)2009
  作者：Dmitriy N. Sokolov、Vladimir V. Zarubaev、Anna A. Shtro、Marina P. Polovinka、Olga A. Luzina、Nina I. Komarova、Nariman F. Salakhutdinov、Oleg I. Kiselev

  DOI：10.1016/j.bmcl.2012.09.084

  日期：2012.12

  anti-inflammatory, antimitotic, antineoplasic, antibacterial, and antimycotic agent. In this work we studied for the first time the antiviral activity of usnic acid and its derivatives against the pandemic influenza virus A(H1N1)pdm09. A total of 26 compounds representing (+) and (−) isomers of usnic acid and their derivates were tested for cytotoxicity and anti-viral activity in MDCK cells by microtetrazolium

  流感是一种广泛的呼吸道感染。每年，它引起流行病，迅速在一个国家到另一个国家传播，甚至流行，涉及地球上很大一部分人口。作为高度可变的感染，流感很容易累积对许多抗病毒药的耐药性突变。 松香酸是一种最初从地衣中分离出来的二苯并呋喃，属于次生代谢产物，具有广泛的生物活性。在人类中，它可以充当消炎药，抗有丝分裂药，抗肿瘤药，抗菌药和抗真菌药。在这项工作中，我们首次研究了松萝酸及其衍生物对大流行性流感病毒A（H1N1）pdm09的抗病毒活性。分别通过微四唑鎓试验和病毒产量试验分别测试了代表松萝酸的（+）和（-）异构体的26种化合物及其衍生物在MDCK细胞中的细胞毒性和抗病毒活性。根据获得的结果，细胞毒性剂量（CTD 50）为50％，有效剂量为50％（ED 50））和每种化合物的选择性指数（SI）。发现其中11个的SI高于10（最高值为37.3）。已证明绝对构型对抗病毒活性具有至关重要的意义。除少数例外
• Synthesis and Biological Activity of Usnic Acid Enamine Derivatives
  作者：O. A. Luzina、D. N. Sokolov、M. A. Pokrovskii、A. G. Pokrovskii、O. B. Bekker、V. N. Danilenko、N. F. Salakhutdinov

  DOI：10.1007/s10600-015-1376-7

  日期：2015.7

  Enamine-derivatives of both enantiomers of usnic acid and the corresponding compounds with a quaternized N atom were synthesized. Compounds 3 and 4 exhibited moderate cytotoxic activity. All quaternized compounds were inactive against the tested tumor cell lines. Quaternized compounds 7 and 8 showed high antimycobacterial activity against Mycobacterium smegmatis, the primary test species for screening antituberculosis drugs. It was shown that the activity dropped in correlation with an increase of the length of the linker between the N atoms. Compound (+)- 8 inhibited effectively the growth of pathogenic Grampositive microorganisms Staphylococcus aureus, S. epidermidis, Streptococcus pneumoniae, and Enterococcus faecalis.

  松萝酸的两个对映体及其与季铵化N原子的相应化合物的衍生物被合成。化合物3和4表现出中等的细胞毒活性。所有季铵化化合物对测试的肿瘤细胞系均无活性。季铵化化合物7和8对用于抗结核药物筛选的主要测试物种——耻垢分枝杆菌显示出高抗分枝杆菌活性。结果表明，活性与N原子之间连接链长度的增加呈下降趋势。化合物（+）-8有效地抑制了病原性革兰氏阳性微生物金黄色葡萄球菌、表皮葡萄球菌、肺炎链球菌和粪肠球菌的生长。
• Synthesis and Biological Evaluation of (+)-Usnic Acid Derivatives as Potential Anti-<i>Toxoplasma gondii</i> Agents
  作者：Hong-Yan Guo、ChunMei Jin、Hai-Ming Zhang、Chun-Mei Jin、Qing-Kun Shen、Zhe-Shan Quan

  DOI：10.1021/acs.jafc.9b02173

  日期：2019.8.28

  Six series of (+)-usnic acid derivatives were synthesized. The IC50 values of these compounds were determined in T. gondii infected HeLa cells (mu M) and in HeLa cells (mu M), and their selectivity indexes (SI) were calculated. In vitro, most of the derivatives tested in this study exhibited more anti activity than that of the parent compound (+)-usnic acid and the positive control drugs. Among these derivatives, methyl (E)-(1-(6-acetyl-7,9-dihydroxy-8,9b-dimethyl-1,3-dioxo-3,9b-dihydrodibenzo[b,d]furan-2(1H)-ylidene)ethyl)phenylalaninate (D3) showed the most effective anti-T. gondii activity (selectivity >2.77). In comparison with the clinically used positive control drugs sulfadiazine (selectivity 1.15), pyrimethamine (selectivity 0.89), spiramycin (selectivity 0.72), and the lead compound (+)-usnic acid (selectivity 0.96), D3 showed better results in vitro. Furthermore, D3 and (E)-6-acetyl-7,9-dihydroxy-8,9b-dimethyl-2-(1-(quinolin-6-ylamino)ethylidene)dibenzo[b,d]furan-1,3-(2H,9bH)-dione (F3) had greater inhibitory effects on T. gondii (inhibition rates 76.0% and 64.6%) in vivo in comparison to spiramycin (inhibition rate 55.2%); in the peritoneal cavity of mice, the number of tachyzoites was significantly reduced (p < 0.001) in vivo. Additionally, some biochemical parameters were measured and spleen indexes were comprehensively evaluated, and the results indicated that mice treated with both compound D3 and compound F3 showed reduced hepatotoxicity and significantly enhanced antioxidative effects in comparison to the normal group. Granuloma and cyst formation were effected by the inhibition of compound D3 and compound F3 in liver sections. Overall, these results indicated that D3 and F3 for use as anti-T. gondii agents are promising lead compounds.