topopyrone D | 308368-86-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: topopyrone D
• 英文别名: 5,7,9-trihydroxy-2-methylnaphtho[2,3-g]chromene-4,6,11-trione
• CAS: 308368-86-7
• 化学式: C₁₈H₁₀O₇
• 分子量: 338.273
• InChiKey: WKOUXLOBNJWENY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  25
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  121
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  乙酸酐 、 topopyrone D 在 吡啶 作用下， 反应 3.0h， 以27%的产率得到topopyrone D triacetate
  参考文献：
  名称：

  拓扑酮的全合成：一类新的拓扑异构酶I毒药。

  摘要：

  拓扑酮代表一类新的高度细胞毒性拓扑异构酶I毒物。该类所有四个自然存在成员的有效总合成已完成。合成的关键元素包括采用两个新型二烯的Diels-Alder反应和钛介导的邻位Friedel-Crafts酰化反应。另外，描述了可从高级中间体获得的两种氯化类似物的合成。

  DOI：

  10.1021/jo702487r
• 作为产物：
  描述：

  N,N-diethyl-2,4-dimethoxybenzamide 在 四甲基乙二胺 、 四丁基氟化铵 、 氢溴酸 、 仲丁基锂 、 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 溶剂黄146 、 乙腈 为溶剂， 反应 1.75h， 生成 topopyrone D
  参考文献：
  名称：

  Total Synthesis of Topopyrones B and D

  摘要：

  We describe a straightforward synthesis of topopyrones B and D, which are potent and selective inhibitors of topoisomerase I. The chemistry should be suitable for additional structure-activity relationship (SAR) work.

  DOI：

  10.1021/ol0617291

文献信息

• Novel Human Topoisomerase I Inhibitors, Topopyrones A, B, C and D. II. Structure Elucidation.
  作者：DAISUKE ISHIYAMA、YOSHINORI KANAI、HISATO SENDA、WAKAO IWATANI、HIROKO TAKAHASHI、HIROSHI KONNO、SUSUMU KANAZAWA

  DOI：10.7164/antibiotics.53.873

  日期：——

  The structures of novel topoisomerase I inhibitors, topopyrones A, B, C and D were elucidated by spectral analysis of the chemical derivatives. These compounds are an anthraquinone type containing a fused 1, 4-pyrone moiety. Topopyrones A and B contain a chlorine atom, however C and D do not. It was suggested that topopyrones B and D are converted from topopyrones A and C, respectively by Wessely-Moser type rearrangement.

  通过对化学衍生物的光谱分析，阐明了新型拓扑异构酶 I 抑制剂拓扑吡喃酮 A、B、C 和 D 的结构。这些化合物属于蒽醌类，含有一个融合的 1，4-吡喃酮分子。拓扑吡喃酮 A 和 B 含有一个氯原子，但 C 和 D 不含氯原子。据认为，拓扑吡喃酮 B 和 D 分别是由拓扑吡喃酮 A 和 C 通过 Wessely-Moser 型重排转化而来的。
• Novel Human Topoisomerase I Inhibitors, Topopyrones A, B, C and D. I. Producing Strain, Fermentation, Isolation, Physico-chemical Properties and Biological Activity.
  作者：YOSHINORI KANAI、DAISUKE ISHIYAMA、HISATO SENDA、WAKAO IWATANI、HIROKO TAKAHASHI、HIROSHI KONNO、SEIJI TOKUMASU、SUSUMU KANAZAWA

  DOI：10.7164/antibiotics.53.863

  日期：——

  In the course of a screening program for specific inhibitors of human topoisomerase I using a recombinant yeast, we have discovered four new active compounds. All four compounds were isolated from the culture broth of a fungus, Phoma sp. BAUA2861, and two of them were isolated from the culture broth of a fungus, Penicillium sp. BAUA4206. We designated these compounds as topopyrones A, B, C and D. Topopyrones A, B, C and D selectively inhibited recombinant yeast growth dependent on expression of human topoisomerase I with IC50 values of 1.22, 0.15, 4.88 and 19.63ng/ml, respectively. The activity and selectivity of topopyrone B were comparable to those of camptothecin. The relaxation of supercoiled pBR322 DNA by human DNA topoisomerase I was inhibited by these compounds, however they did not inhibit human DNA topoisomerase II. Topopyrones A, B, C and D were cytotoxic to all tumor cell lines when tested in vitro. Topopyrone B has potent inhibitory activity against herpesvirus, especially varicella zoster virus (VZV). It inhibited VZV growth with EC50 value of 0.038μg/ml, which is 24-fold stronger than that of acyclovir (0.9μg/rnl). Topopyrones A, B, and C were inhibitory to Grampositive bacteria.

  在利用重组酵母筛选人类拓扑异构酶I特异性抑制剂的过程中，我们发现了四种新的活性化合物。这四种化合物都是从真菌Phoma sp. BAUA2861的培养液中分离出来的，其中两种是从真菌Penicillium sp. BAUA4206的培养液中分离出来的。我们将这些化合物命名为拓扑霉素A、B、C和D。拓扑霉素A、B、C和D分别以1.22、0.15、4.88和19.63ng/ml的IC50值选择性抑制了依赖人类拓扑异构酶I表达的重组酵母生长。拓扑霉素B的活性和选择性堪比喜树碱。这些化合物抑制了人类DNA拓扑异构酶I对超螺旋pBR322 DNA的松弛作用，但它们并不抑制人类DNA拓扑异构酶II。体外测试表明，拓扑霉素A、B、C和D对所有肿瘤细胞系都有细胞毒性。拓扑霉素B对疱疹病毒，尤其是水痘带状疱疹病毒（VZV）有很强的抑制活性。它以0.038μ
• METHODS, COMPOSITIONS, AND KITS FOR THE TREATMENT OF CANCER
  申请人：Haggerty Timothy J.

  公开号：US20140335050A1

  公开（公告）日：2014-11-13

  The invention features methods, compositions, and kits for the administration of an HSP90 inhibitor, OBAA, flunarizine, aphidicolin, damnacanthal, dantrolene, or an analog thereof, alone, or in combination with, e.g., a TAA, an antigen-binding scaffold (e.g., an antibody, a soluble T cell receptor, or a chimeric receptor) specific for a TAA, a cell (e.g., a white blood cell that targets a cancer cell), and/or an IFN-β receptor agonist or an IFN-γ receptor agonist, for the treatment of cancer.
• Total Synthesis of Topopyrones B and D
  作者：Jason Samuel Tan、Marco A. Ciufolini

  DOI：10.1021/ol0617291

  日期：2006.10.1

  We describe a straightforward synthesis of topopyrones B and D, which are potent and selective inhibitors of topoisomerase I. The chemistry should be suitable for additional structure-activity relationship (SAR) work.
• Total Synthesis of the Topopyrones:  A New Class of Topoisomerase I Poisons
  作者：Mark A. Elban、Sidney M. Hecht

  DOI：10.1021/jo702487r

  日期：2008.2.1

  The topopyrones represent a new class of highly cytotoxic topoisomerase I poisons. Efficient total syntheses of all four naturally occurring members of this class have been accomplished. Key elements of the syntheses include Diels−Alder reactions employing two novel dienes and a titanium-mediated ortho-directed Friedel−Crafts acylation. Additionally, the syntheses of two chlorinated analogues accessible

  拓扑酮代表一类新的高度细胞毒性拓扑异构酶I毒物。该类所有四个自然存在成员的有效总合成已完成。合成的关键元素包括采用两个新型二烯的Diels-Alder反应和钛介导的邻位Friedel-Crafts酰化反应。另外，描述了可从高级中间体获得的两种氯化类似物的合成。