(3R,4R,5R)-1-Oxo-2,2-difluoro-3α-acetoxy-4α-<<(tert-butyldiphenylsilyl)oxy>methyl>-5α-<(benzyloxy)methyl>-1,5-oxidopentane | 151636-34-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (3R,4R,5R)-1-Oxo-2,2-difluoro-3α-acetoxy-4α-<<(tert-butyldiphenylsilyl)oxy>methyl>-5α-<(benzyloxy)methyl>-1,5-oxidopentane
• CAS: 151636-34-9
• 化学式: C₃₂H₃₆F₂O₆Si
• 分子量: 582.717
• InChiKey: JGIWMKWVBNRARP-SSBOKUKZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.89
• 重原子数：
  41.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  71.06
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (3R,4R,5R)-1-Oxo-2,2-difluoro-3α-acetoxy-4α-<<(tert-butyldiphenylsilyl)oxy>methyl>-5α-<(benzyloxy)methyl>-1,5-oxidopentane 在 吡啶 、 sodium tetrahydroborate 、 碳酸氢钠 、 potassium carbonate 、 sodium iodide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.33h， 生成 (1R,3R,4R,5R)-4α-<<(tert-Butyldiphenylsilyl)oxy>methyl>-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
• 作为产物：
  描述：

  (2R,3S)-1-<(tert-Butyldiphenylsilyl)oxy>-2-formyl-3-(mesyloxy)-4-(benzyloxy)butane 在 吡啶 、 cesium acetate 、 锌 作用下， 以 四氢呋喃 、 乙二醇二甲醚 为溶剂， 反应 34.5h， 生成 (3R,4R,5R)-1-Oxo-2,2-difluoro-3α-acetoxy-4α-<<(tert-butyldiphenylsilyl)oxy>methyl>-5α-<(benzyloxy)methyl>-1,5-oxidopentane
  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