(1R,3R,4R,5R)-4α-(Cyanomethyl)-5α-<(benzyloxy)methyl>-7,7-difluoro-2,6-dioxa<3.1.1>bicycloheptane | 151567-21-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1R,3R,4R,5R)-4α-(Cyanomethyl)-5α-<(benzyloxy)methyl>-7,7-difluoro-2,6-dioxa<3.1.1>bicycloheptane
• CAS: 151567-21-4
• 化学式: C₁₅H₁₅F₂NO₃
• 分子量: 295.286
• InChiKey: MNKDCMONIMWPMA-XJFOESAGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.49
• 重原子数：
  21.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  51.48
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (1R,3R,4R,5R)-4α-(Cyanomethyl)-5α-<(benzyloxy)methyl>-7,7-difluoro-2,6-dioxa<3.1.1>bicycloheptane 在 palladium on activated charcoal 4-二甲氨基吡啶 、 氢气 、 sodium hexamethyldisilazane 、 二异丁基氢化铝 、 三乙胺 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 49.5h， 生成 (E)-7-[(1R,3R,4R,5R)-3-(tert-Butyl-dimethyl-silanyloxymethyl)-7,7-difluoro-2,6-dioxa-bicyclo[3.1.1]hept-4-yl]-hept-5-enoic acid
  参考文献：
  名称：

  Synthesis of a thromboxane A2 receptor antagonist possessing the dioxabicycloheptane nucleus of TXA2

  摘要：

  The synthesis of the TXA2/PGH2 receptor antagonist 6 from the known chiral intermediate (-)-8 is described. The critical reaction is the inversion of C-5 in 11a and 11b by an intramolecular cyclization reaction induced by nucleophilic reagents as shown in structure 13a. The key intermediate 22 was prepared in 26.5 % yield in five steps. Diastereoselectivity is high in all but one of the steps, the Reformatsky reaction, which leads to equal amounts of 11a and 11b. The design of 6 is based on the dioxabicycloheptane nucleus characteristic of TXA2 (1), which has been stabilized by fluorination. To this nucleus the two side chains are attached in cis orientation, and the omega-chain is modified as reported for the receptor antagonist (-)-5, which in turn is an analogue of PGH2 (3). These changes in the side chains have the effect of converting the powerful agonist 2 (DFTXA2) into a receptor antagonist devoid of agonist activity, which binds to the receptor with nanomolar affinity. These findings lend support to the view of a single TXA2/PGH2 receptor.

  DOI：

  10.1021/jo00073a035
• 作为产物：
  描述：

  氰化钠 、 (1R,3R,4R,5R)-4α-<<(Methanesulfonyl)oxy>methyl>-5α-<(benzyloxy)methyl>-7,7-difluoro-2,6-dioxa<3.1.1>bicycloheptane 以 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 (1R,2R,6R,8R)-10,10-Difluoro-4,7,9-trioxa-tricyclo[6.1.1.0^2,6]decane 、 (1R,3R,5R)-3-Benzyloxymethyl-7,7-difluoro-4-methylene-2,6-dioxa-bicyclo[3.1.1]heptane 、 (1R,3R,4R,5R)-4α-(Cyanomethyl)-5α-<(benzyloxy)methyl>-7,7-difluoro-2,6-dioxa<3.1.1>bicycloheptane
  参考文献：
  名称：

  Synthesis of a thromboxane A2 receptor antagonist possessing the dioxabicycloheptane nucleus of TXA2

  摘要：

  The synthesis of the TXA2/PGH2 receptor antagonist 6 from the known chiral intermediate (-)-8 is described. The critical reaction is the inversion of C-5 in 11a and 11b by an intramolecular cyclization reaction induced by nucleophilic reagents as shown in structure 13a. The key intermediate 22 was prepared in 26.5 % yield in five steps. Diastereoselectivity is high in all but one of the steps, the Reformatsky reaction, which leads to equal amounts of 11a and 11b. The design of 6 is based on the dioxabicycloheptane nucleus characteristic of TXA2 (1), which has been stabilized by fluorination. To this nucleus the two side chains are attached in cis orientation, and the omega-chain is modified as reported for the receptor antagonist (-)-5, which in turn is an analogue of PGH2 (3). These changes in the side chains have the effect of converting the powerful agonist 2 (DFTXA2) into a receptor antagonist devoid of agonist activity, which binds to the receptor with nanomolar affinity. These findings lend support to the view of a single TXA2/PGH2 receptor.

  DOI：

  10.1021/jo00073a035