6,7-demethylenedeoxypodophyllotoxin | 1173-42-8

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 木脂素内酯
• 英文名称: 6,7-demethylenedeoxypodophyllotoxin
• 英文别名: (3aR,4R,9aR)-6,7-dihydroxy-4-(3,4,5-trimethoxyphenyl)-3a,4,9,9a-tetrahydro-1H-benzo[f]isobenzofuran-3-one；(3aR,4R,9aR)-6,7-dihydroxy-4-(3,4,5-trimethoxyphenyl)-3a,4,9,9a-tetrahydro-1H-benzo[f][2]benzofuran-3-one
• CAS: 1173-42-8
• 化学式: C₂₁H₂₂O₇
• 分子量: 386.401
• InChiKey: RINWQCSDWSZGDJ-RQUSPXKASA-N

物化性质

• 熔点：
  236-238 °C
• 沸点：
  611.2±55.0 °C(Predicted)
• 密度：
  1.327±0.06 g/cm3(Predicted)
• 溶解度：
  二氯甲烷；乙酸乙酯;甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  94.4
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6,7-demethylenedeoxypodophyllotoxin 在 N-溴代丁二酰亚胺(NBS) 、 cesium fluoride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 (-)-β-peltatin-A-methyl ether
  参考文献：
  名称：

  Yamaguchi, Hideo; Nakajima, Syunji; Arimoto, Masao, Chemical and pharmaceutical bulletin, 1984, vol. 32, # 5, p. 1754 - 1760

  摘要：

  DOI：
• 作为产物：
  描述：

  去氧鬼臼毒素 在 lead(IV) acetate 作用下， 以 溶剂黄146 为溶剂， 反应 3.0h， 以15 mg的产率得到6,7-demethylenedeoxypodophyllotoxin
  参考文献：
  名称：

  Isolation of 6,7-Demethylenedesoxypodophyllotoxin from Hernandia ovigera.

  摘要：

  从台湾采集的 Hernandia ovigera L.（Hernandiaceae）种子中分离出了 6，7-Demethylenedesoxypodophyllotoxin（1）以及几种已知的木脂素。这是首次在天然来源中发现 1 的实例。此外，还通过二维 H-C 相关光谱（COSY）和 H-C 长程 COSY 技术，确定了从该植物中分离出的几种豆荚毒素类似物的 13C 核磁共振信号的分配。

  DOI：

  10.1248/cpb.40.1318

文献信息

• Isolation, Semisynthesis, and Molecular Modeling of Deoxypodophyllotoxin Analogs for an Anti‐oral Cancer Agent
  作者：Eunae Kim、Hyun Jung Kim、Seung‐Sik Cho、Jung‐Hyun Shim、Goo Yoon

  DOI：10.1002/bkcs.11979

  日期：2020.4

  The predicted binding pose of DPT in soluble tubulin and 3‐dimensional structures of the ligands such as DPT, PT, Model 1, and Model 2.

  DPT在可溶性微管蛋白和配体的三维结构（如DPT，PT，模型1和模型2）中的预测结合姿势。
• Antitumor Agents. I. DNA Topoisomerase II Inhibitory Activity and the Structural Relationship of Podophyllotoxin Derivatives as Antitumor Agents.
  作者：Tadafumi TERADA、Katsuhiko FUJIMOTO、Makoto NOMURA、Jun-ichi YAMASHITA、Takashi KOBUNAI、Setsuo TAKEDA、Konstanty WIERZBA、Yuji YAMADA、Hideo YAMAGUCHI

  DOI：10.1248/cpb.40.2720

  日期：——

  Various podophyllotoxin derivatives from desoxypodophyllotoxin (DPT) were synthesized to examine the structural relationships between the biological significance (cytotoxic effect, effects on DNA topoisomerase II and tubulin polymerization) in vitro and antitumor activity in vivo (L 1210).An intact 6, 7-methylenedioxy group of DPT is necessary to inhibit tubulin polymerization and topoisomerase II. 4'-Phenolic hydroxyl group of DPT is essential to inhibit DNA topoisomerase II and the inhibitory effect on DNA topoisomerase II contributes to a high cytotoxicity.The introduction of an aminoalkoxy group at 1-position of DPT enhances the inhibitory activity against DNA topoisomerase II and cytotoxic effect, causing the inhibitory activity against tubulin polymerization to disappear. The results of antitumor test in mice bearing L 1210 on podophyllotoxin derivatives suggest the following : 1) the strong cytotoxic effect itself is not a good indication of antitumor activity in vivo as long as it is associated with inhibition of tubulin polymerization. DNA topoisomerase II inhibitory effect contributes to an antitumor activity in vivo; 2) detailed measurements of cytotoxicity and inhibition on DNA topoisomerase II and tubulin polymerization in vitro are necessary to evaluate podophyllotoxin derivatives.

  合成了多种来自脱氧髓鞘素（DPT）的紫苑毒素衍生物，以研究其在体外的生物重要性（细胞毒性、对 DNA 拓扑异构酶 II 的影响和微管聚合影响）与在体内的抗肿瘤活性（L 1210）之间的结构关系。DPT 的完整 6, 7-亚甲基二氧基基团是抑制微管聚合和拓扑异构酶 II 所必需的。DPT 的 4'-酚羟基对于抑制 DNA 拓扑异构酶 II 是必不可少的，而对 DNA 拓扑异构酶 II 的抑制作用导致了高细胞毒性。DPT 在 1 位置引入氨基烷氧基团增强了对 DNA 拓扑异构酶 II 的抑制活性和细胞毒性，导致对微管聚合的抑制活性消失。在 L 1210 移植小鼠中对紫苑毒素衍生物的抗肿瘤测试结果表明：1）只要与抑制微管聚合相关，强细胞毒性本身并不是评估体内抗肿瘤活性的良好指征。DNA 拓扑异构酶 II 的抑制作用对体内抗肿瘤活性有贡献；2）为了评估紫苑毒素衍生物，需详细测定体外的细胞毒性及对 DNA 拓扑异构酶 II 和微管聚合的抑制作用。
• Synthesis and cytotoxicity of podophyllotoxin analogues modified in the A ring
  作者：A Castro

  DOI：10.1016/s0223-5234(02)00007-7

  日期：2003.1

  Several podophyllotoxin derivatives lacking the methylenedioxy group or with different functionalization of the A-ring of the cyclolignan skeleton have been prepared and evaluated for their cytotoxic activities on four neoplastic cell lines (P-388, A-549, HT-29 and MEL-28). Most of them maintained their cytotoxicity at the microM level.

  已经制备了几种缺乏亚甲二氧基或环木脂素骨架的A环功能不同的鬼臼毒素衍生物，并评估了它们对四种肿瘤细胞系（P-388，A-549，HT-29和MEL-28）的细胞毒活性）。他们中的大多数保持其细胞毒性在microM水平。
• Use of small molecule compounds for immunopotentiation
  申请人：Valiante M. Nicholas

  公开号：US20050136065A1

  公开（公告）日：2005-06-23

  The invention provides immunostimulatory compositions comprising a small molecule immuno-poteniator (SMIP) compound and methods of administration thereof. Also provided are methods of administering a SMIP compound in an effective amount to enhance the immune response of a subject to an antigen. Further provided are novel compositions and methods of administering SMIP compounds alone or in combination with another agent for the treatment of cancer, infectious diseases and/or allergies/asthma.

  本发明提供了包含小分子免疫增强剂（SMIP）化合物的免疫刺激组合物及其给药方法。还提供了在有效剂量下给予SMIP化合物以增强受体对抗原的免疫反应的方法。此外，还提供了用于治疗癌症、传染性疾病和/或过敏/哮喘的新型组合物和给药SMIP化合物的方法，单独或与另一种药物联合使用。
• Severe acute respiratory syndrome coronavirus
  申请人：Rappuoli Rino

  公开号：US20060257852A1

  公开（公告）日：2006-11-16

  An outbreak of a virulent respiratory virus, now known as Severe Acute Respiratory Syndrome (SARS), was identified in Hong Kong, China and a growing number of countries around the world in 2003. The invention relates to nucleic acids and proteins from the SARS coronavirus. These nucleic acids and proteins can be used in the preparation and manufacture of vaccine formulations, diagnostic reagents, kits, etc. The invention also provides methods for treating SARS by administering small molecule antiviral compounds, as well as methods of identifying potent small molecules for the treatment of SARS.

  2003年，在中国香港和世界各地越来越多的国家中，爆发了一种名为严重急性呼吸综合症（SARS）的致命呼吸道病毒。本发明涉及来自SARS冠状病毒的核酸和蛋白质。这些核酸和蛋白质可以用于制备和制造疫苗配方、诊断试剂盒等。本发明还提供了通过给予小分子抗病毒化合物治疗SARS的方法，以及识别用于治疗SARS的有效小分子的方法。