TDR-9706 | 185418-56-8

• 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: TDR-9706
• 英文别名: (1S,4R,5R,8R,9R,10R,12R,13R)-1,5,9-trimethyl-10-(trifluoromethyl)-11,14,15,16-tetraoxatetracyclo[10.3.1.0^4,13.0^8,13]hexadecan-10-ol；10α-(trifluoromethyl)hydroartemisinin；10β-hydroxy-10α-trifluoromethyl-deoxoartemisinin；12α-trifluoromethyl-hydroartemisinin；Tfmha；(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-10-(trifluoromethyl)-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-ol
• CAS: 185418-56-8
• 化学式: C₁₆H₂₃F₃O₅
• 分子量: 352.351
• InChiKey: QPGCYSREBONXHE-ISOSDAIHSA-N

物化性质

• 沸点：
  372.3±42.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  TDR-9706 在 二溴亚砜 、 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以86%的产率得到10-bromo-1,5,9-trimethyl-10-(trifluoromethyl)-11,14,15,16-tetraoxatetracyclo[10.3.1.0^4,13.0^8,13]hexadecane
  参考文献：
  名称：

  First Synthesis of 10α-(Trifluoromethyl)deoxoartemisinin

  摘要：

  [GRAPHICS]A novel, nonacetal (trifluoromethyl)deoxoartemisinin was prepared with good stereoselectivity. This compound was obtained by debromination of the 10alpha-CF3-10-bromodeoxoartemisinin in the presence of tributyltin hydride at reflux in toluene without alteration of the endoperoxide bridge. It presented a reasonable antimalarial activity.

  DOI：

  10.1021/ol017227z
• 作为产物：
  描述：

  青蒿素 、 (三氟甲基)三甲基硅烷 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 25.0h， 以87%的产率得到TDR-9706
  参考文献：
  名称：

  Synthesis and in vivo antimatarial activity of 12α-trifluoromethyl-hydroartemisinin

  摘要：

  12 alpha-Trifluoromethyl-hydroartemisinin 4 was selectively prepared from the reaction of artemisinin 1 with TMSCF(3) in good yields. The alpha configuration of the CF3 substituent was established by NMR experiments. Compound 4 exhibits a better antimalarial activity against Plasmodium vinckei in mice, than artemisinin. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/s0960-894x(96)00488-x

文献信息

• Preparation of 10-Trifluoromethyl Artemether and Artesunate. Influence of Hexafluoropropan-2-ol on Substitution Reaction
  作者：Guillaume Magueur、Benoit Crousse、Michèle Ourévitch、Jean-Pierre Bégué、Danièle Bonnet-Delpon

  DOI：10.1021/jo035174o

  日期：2003.12.1

  10-trifluoromethyl analogues of important antimalarials such as artemether and artesunate, the substitution reaction of the 10-trifluoromethyl hemiketal 6 and bromide 4 derived from artemisinin was investigated. While 6 appeared to be unreactive under various conditions, bromide 4 could easily undergo substitution with methanol under electrophilic assistance or noncatalyzed conditions. Optimization of the

  为了制备重要抗疟药例如蒿甲醚和青蒿琥酯的10-三氟甲基类似物，研究了由青蒿素衍生的10-三氟甲基半缩酮6和溴化物4的取代反应。尽管6在各种条件下似乎都没有反应性，但溴化4在亲电子助剂或非催化条件下很容易被甲醇取代。反应的优化揭示了CH（2）Cl（2）作为溶剂的作用，以避免竞争性消除过程，以及六氟-2-丙醇（HFIP）在增加取代反应的速率和立体选择性方面的关键影响（de > 98％）。该反应的效率以各种醇和羧酸盐为例（产率高达89％）。
• Alkylation of manganese(II) tetraphenylporphyrin by antimalarial fluorinated artemisinin derivatives
  作者：Montserrat Rodriguez、Danièle Bonnet-Delpon、Jean-Pierre Bégué、Anne Robert、Bernard Meunier

  DOI：10.1016/s0960-894x(03)00076-3

  日期：2003.3

  The alkylating properties of two artemisinin derivatives bearing a trifluoromethyl substituent at C10 were evaluated toward manganese(II) tetraphenylporphyrin, considered as a heme model. Chlorin-type covalent adducts were obtained by alkylation of the porphyrin ring by C-centered radicals derived from reductive activation of the peroxide function of the drugs.

  对 C10 处带有三氟甲基取代基的两种青蒿素衍生物的烷基化特性进行了评估，锰 (II) 四苯基卟啉被视为血红素模型。Chlorin 型共价加合物是通过卟啉环被 C 中心自由基烷基化获得的，这些自由基来源于药物的过氧化物功能的还原活化。
• Synthesis and in vivo antimatarial activity of 12α-trifluoromethyl-hydroartemisinin
  作者：Ahmed Abouabdellah、Jean-Pierre Bégué、Danièle Bonnet-Delpon、Jean-Charles Gantier、Truong Thi Thanh Nga、Truong Dinh Thac

  DOI：10.1016/s0960-894x(96)00488-x

  日期：1996.11

  12 alpha-Trifluoromethyl-hydroartemisinin 4 was selectively prepared from the reaction of artemisinin 1 with TMSCF(3) in good yields. The alpha configuration of the CF3 substituent was established by NMR experiments. Compound 4 exhibits a better antimalarial activity against Plasmodium vinckei in mice, than artemisinin. Copyright (C) 1996 Elsevier Science Ltd
• First Synthesis of 10α-(Trifluoromethyl)deoxoartemisinin
  作者：Fatima Chorki、Fabienne Grellepois、Benoit Crousse、Vu Dinh Hoang、Nguyen Van Hung、Danièle Bonnet-Delpon、Jean-Pierre Bégué

  DOI：10.1021/ol017227z

  日期：2002.3.1

  [GRAPHICS]A novel, nonacetal (trifluoromethyl)deoxoartemisinin was prepared with good stereoselectivity. This compound was obtained by debromination of the 10alpha-CF3-10-bromodeoxoartemisinin in the presence of tributyltin hydride at reflux in toluene without alteration of the endoperoxide bridge. It presented a reasonable antimalarial activity.