(1aR,7aS,10aS,10bS,E)-1a-methyl-8-methylene-5-(trifluoromethyl)-2,3,6,7,7a,8,10a,10b-octahydrooxireno[2′,3′:9,10]cyclodeca[1,2-b]furan-9(1aH)-one

• 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: (1aR,7aS,10aS,10bS,E)-1a-methyl-8-methylene-5-(trifluoromethyl)-2,3,6,7,7a,8,10a,10b-octahydrooxireno[2′,3′:9,10]cyclodeca[1,2-b]furan-9(1aH)-one
• 英文别名: (1S,2S,4R,7E,11S)-4-methyl-12-methylidene-8-(trifluoromethyl)-3,14-dioxatricyclo[9.3.0.02,4]tetradec-7-en-13-one
• 化学式: C₁₅H₁₇F₃O₃
• 分子量: 302.293
• InChiKey: ALOGSSVOBMQLMA-HIMZRUBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (E)-6-(tert-butyldiphenylsilyloxy)-3-methylhex-2-en-1-ol 在 吡啶 、 盐酸 、 manganese(IV) oxide 、 lithium aluminium tetrahydride 、 正丁基锂 、 hexaammonium heptamolybdate tetrahydrate 、 四丁基氟化铵 、 双氧水 、 叔丁基锂 、 sodium hexamethyldisilazane 、 4-甲基苯磺酸吡啶 、 碳酸氢钠 、 戴斯-马丁氧化剂 、 间氯过氧苯甲酸 、 六甲基二硅氮烷 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 45.91h， 生成 (1aR,7aS,10aS,10bS,E)-1a-methyl-8-methylene-5-(trifluoromethyl)-2,3,6,7,7a,8,10a,10b-octahydrooxireno[2′,3′:9,10]cyclodeca[1,2-b]furan-9(1aH)-one
  参考文献：
  名称：

  Syntheses and Biological Evaluation of Costunolide, Parthenolide, and Their Fluorinated Analogues

  摘要：

  Inspired by the biosynthesis of sesquiterpene lactones (SLs), herein we report the asymmetric total synthesis of the germacrane ring (24). The synthetic strategy features a selective aldol reaction between beta,gamma-unsaturated chiral sulfonylamide 15a and aldehyde 13, as well as the intramolecular alpha-alkylation of sulfone 21 to construct a 10-membered carbocylic ring. The key intermediate 24 can be used to prepare the natural products costunolide and parthenolide (PTL), which are the key precursors for transformation into other SLs. Furthermore, the described synthetic sequences are amenable to the total synthesis of SL analogues, such as trifluoro-methylated analogues 32 and 45. Analogues 32 and 45 maintained high activities against a series of cancer cell lines compared to their parent PTL and costunolide, respectively. In addition, 32 showed enhanced tolerance to acidic media compared with PTL. To our surprise, PTL and 32 showed comparable half-lives in rat plasma and in the presence of human liver microsomes.

  DOI：

  10.1021/acs.jmedchem.5b00915

文献信息

• Syntheses and Biological Evaluation of Costunolide, Parthenolide, and Their Fluorinated Analogues
  作者：Zhong-Jin Yang、Wei-Zhi Ge、Qiu-Ying Li、Yaxin Lu、Jian-Miao Gong、Bei-Jia Kuang、Xiaonan Xi、Haiting Wu、Quan Zhang、Yue Chen

  DOI：10.1021/acs.jmedchem.5b00915

  日期：2015.9.10

  Inspired by the biosynthesis of sesquiterpene lactones (SLs), herein we report the asymmetric total synthesis of the germacrane ring (24). The synthetic strategy features a selective aldol reaction between beta,gamma-unsaturated chiral sulfonylamide 15a and aldehyde 13, as well as the intramolecular alpha-alkylation of sulfone 21 to construct a 10-membered carbocylic ring. The key intermediate 24 can be used to prepare the natural products costunolide and parthenolide (PTL), which are the key precursors for transformation into other SLs. Furthermore, the described synthetic sequences are amenable to the total synthesis of SL analogues, such as trifluoro-methylated analogues 32 and 45. Analogues 32 and 45 maintained high activities against a series of cancer cell lines compared to their parent PTL and costunolide, respectively. In addition, 32 showed enhanced tolerance to acidic media compared with PTL. To our surprise, PTL and 32 showed comparable half-lives in rat plasma and in the presence of human liver microsomes.