(3R,3'R,5aS,5'aS,6R,6'R,8aS,8'aS,9R,9'R,10S,10'S,12R,12'R,12aR,12'aR)-10,10'-[2-keto-1,3-propanediylbis(oxy)]bis[decahydro-3,6,9-trimethyl-3,12-epoxy-12H-pyrano[4,3-j]-1,2-benzodioxepin]

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (3R,3'R,5aS,5'aS,6R,6'R,8aS,8'aS,9R,9'R,10S,10'S,12R,12'R,12aR,12'aR)-10,10'-[2-keto-1,3-propanediylbis(oxy)]bis[decahydro-3,6,9-trimethyl-3,12-epoxy-12H-pyrano[4,3-j]-1,2-benzodioxepin]
• 英文别名: NSC 722593；1,3-bis[[(1S,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]oxy]propan-2-one
• 化学式: C₃₃H₅₀O₁₁
• 分子量: 622.753
• InChiKey: YWDPFBADBFDYTD-YRMPQYJJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  44
• 可旋转键数：
  6
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  109
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (3R,3'R,5aS,5'aS,6R,6'R,8aS,8'aS,9R,9'R,10S,10'S,12R,12'R,12aR,12'aR)-10,10'-[2-keto-1,3-propanediylbis(oxy)]bis[decahydro-3,6,9-trimethyl-3,12-epoxy-12H-pyrano[4,3-j]-1,2-benzodioxepin] 在 盐酸羟胺 、 sodium acetate 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 N-[1,3-bis[[(1S,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]oxy]propan-2-ylidene]hydroxylamine
  参考文献：
  名称：

  [EN] ANTICANCER AND ANTIPROTOZOAL DIHYDROARTEMISINENE AND DIHYDROARTEMISITENE DIMERS WITH DESIRABLE CHEMICAL FUNCTIONALITIES
  [FR] DIMERES DIHYDROARTEMISINENE ET DIHYDROARTEMISITENE ANTICANCEREUX ET ANTIPROTOZOAIRES A FONCTIONNALITES CHIMIQUES DESIREES

  摘要：

  这项发明包括含有二氢青蒿素和二氢青蒿素二聚体的组合物，具有抗癌或抗癌转移剂以及抗原虫，包括抗疟疾和抗利什曼病属性。该发明还描述了这些组合物的制备方法以及利用这些组合物治疗癌症或预防癌症转移以及原虫感染，包括疟疾或利什曼病的方法。该发明的化合物代表了一种潜在的新型抗肿瘤或抗转移剂类，已显示出对实体肿瘤具有良好活性。

  公开号：

  WO2006002105A1
• 作为产物：
  描述：

  1,3-二羟基丙酮 、 dihydroartesiminin 在 三氟化硼乙醚 作用下， 以 乙醚 为溶剂， 以45.1%的产率得到(3R,3'R,5aS,5'aS,6R,6'R,8aS,8'aS,9R,9'R,10S,10'S,12R,12'R,12aR,12'aR)-10,10'-[2-keto-1,3-propanediylbis(oxy)]bis[decahydro-3,6,9-trimethyl-3,12-epoxy-12H-pyrano[4,3-j]-1,2-benzodioxepin]
  参考文献：
  名称：

  Synthesis and evaluation of dihydroartemisinin and dihydroartemisitene acetal dimers showing anticancer and antiprotozoal activity

  摘要：

  Twelve artemisinin acetal dimers were synthesized and tested for antitumor activity in the National Cancer Institute (NCI) in vitro human tumor 60 cell line assay, producing a mean GI(50) concentration between 8.7 (least active) and 0.019 mu M (most active). The significant activity of the compounds in this preliminary screen led to additional in vitro antitumor and antiangiogenesis studies. Several active dimers were also evaluated in the in vivo NCI hollow fiber assay followed by a preliminary xenograft study. The title compounds were found to be active against solid tumor-derived cell lines and showed good correlation with other artemisinin-based molecules in the NCI database. The dimers were also evaluated for their antimalarial and antileishmanial activities. The antimalarial activity ranged from 0.3 to 32 nM (IC50), compared to 9.9 nM for artemisinin. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.11.050

文献信息

• [EN] ANTICANCER AND ANTIPROTOZOAL DIHYDROARTEMISINENE AND DIHYDROARTEMISITENE DIMERS WITH DESIRABLE CHEMICAL FUNCTIONALITIES<br/>[FR] DIMERES DIHYDROARTEMISINENE ET DIHYDROARTEMISITENE ANTICANCEREUX ET ANTIPROTOZOAIRES A FONCTIONNALITES CHIMIQUES DESIREES
  申请人：UNIV MISSISSIPPI

  公开号：WO2006002105A1

  公开（公告）日：2006-01-05

  This invention comprises compositions containing dihydroartemisinin- and dihydroartemisitene- dimers with activity as anticancer or anticancer metastasis agents and anti-protozal, including anti-malarial and anti-leishmanial properties. This invention also describes methods of preparation of these compositions and methods of use of such compositions for the treatment of cancer or prevention of cancer metastasis, and protozoal infections, including malaria, or leishmaniasis. The compounds of this invention represent a potential new class of anti-tumor or anti-metastasis agents, one that has shown promising activity against solid tumors.

  这项发明包括含有二氢青蒿素和二氢青蒿素二聚体的组合物，具有抗癌或抗癌转移剂以及抗原虫，包括抗疟疾和抗利什曼病属性。该发明还描述了这些组合物的制备方法以及利用这些组合物治疗癌症或预防癌症转移以及原虫感染，包括疟疾或利什曼病的方法。该发明的化合物代表了一种潜在的新型抗肿瘤或抗转移剂类，已显示出对实体肿瘤具有良好活性。
• Synthesis and evaluation of dihydroartemisinin and dihydroartemisitene acetal dimers showing anticancer and antiprotozoal activity
  作者：Ahmed M. Galal、Waseem Gul、Desmond Slade、Samir A. Ross、Shixia Feng、Melinda G. Hollingshead、Michael C. Alley、Gurmeet Kaur、Mahmoud A. ElSohly

  DOI：10.1016/j.bmc.2008.11.050

  日期：2009.1

  Twelve artemisinin acetal dimers were synthesized and tested for antitumor activity in the National Cancer Institute (NCI) in vitro human tumor 60 cell line assay, producing a mean GI(50) concentration between 8.7 (least active) and 0.019 mu M (most active). The significant activity of the compounds in this preliminary screen led to additional in vitro antitumor and antiangiogenesis studies. Several active dimers were also evaluated in the in vivo NCI hollow fiber assay followed by a preliminary xenograft study. The title compounds were found to be active against solid tumor-derived cell lines and showed good correlation with other artemisinin-based molecules in the NCI database. The dimers were also evaluated for their antimalarial and antileishmanial activities. The antimalarial activity ranged from 0.3 to 32 nM (IC50), compared to 9.9 nM for artemisinin. (C) 2008 Elsevier Ltd. All rights reserved.