ethyl (E)-4-(adenin-N⁹-yl)-2-fluoro-3-butenoate | 162106-19-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: ethyl (E)-4-(adenin-N⁹-yl)-2-fluoro-3-butenoate
• 英文别名: ethyl (E)-4-(6-aminopurin-9-yl)-2-fluorobut-3-enoate
• CAS: 162106-19-6
• 化学式: C₁₁H₁₂FN₅O₂
• 分子量: 265.247
• InChiKey: DHTVWJIRWPYGMC-ONEGZZNKSA-N

物化性质

• 沸点：
  512.2±60.0 °C(predicted)
• 密度：
  1.47±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  95.9
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl (E)-4-(adenin-N⁹-yl)-2-fluoro-3-butenoate 在 敌草腈 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 ethyl (E)-4-(adenin-N⁹-yl)-2-fluoro-2-butenoate 、 ethyl (Z)-4-(adenin-N⁹-yl)-2-fluoro-2-butenoate
  参考文献：
  名称：

  Unsaturated Acyclic Analogs of 2'-Deoxyadenosine and Thymidine Containing Fluorine: Synthesis and Biological Activity

  摘要：

  The syntheses and biological activities of fluorobutynol 11 and (E)- and (Z)-fluorobutenols 8a,d and 9a,d are described. Alkylation of adenine with bromofluorobutyne 13a afforded intermediate 14 which was converted to fluorobutynol 11. Aldehyde 16a and (carbothoxyfluoromethyl)triphenylphosphonium bromide furnished (E)- and (Z)-fluorobutenoates 19a and 20a accompanied by regioisomer 21a. A similar reaction of compound 16d afforded Z- and E-esters 19d and 20d. Reduction of the mixture of 19a and 20a with DIBALH gave (E)- and (Z)-fluoroalkenols 8a and 9a. Similarly, the Z-ester 19d gave (Z)-fluoroalkenol 9d. Both 19d and 20d were reduced with NaBH4 to give (Z)- and (E)-fluoroalkenols 9d and 8d. Hydrogenation of 19a and 20a afforded fluoro ester 23. A similar reduction of 8a and 9a led to fluoro alcohol 24 and the defluorinated product 25 which were separated by chromatography on a Bio-Rad AG 1-X2 (OH-) column. (Z)-Fluorobutenol 9a is a substrate for adenosine deaminase, whereas the E-isomer 8a is inert toward the enzyme. By contrast, analogue 8a inhibited the replication and cytopathic effect of HN-1 in ATH8 cells with an IC50 Of approximately 100 mu M, but the Z-isomer 9a was inactive. This effect was accompanied by 36% cytotoxicity at 100 mu M. Compounds 11 and 8d inhibited the growth of murine leukemia L1210 culture with IC50 = 89 and 60 mu M, respectively.

  DOI：

  10.1021/jm00006a004
• 作为产物：
  描述：

  N9-(2,2-二乙氧基乙基)腺嘌呤 在 盐酸 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 17.0h， 生成 ethyl (E)-4-(adenin-N⁹-yl)-2-fluoro-3-butenoate
  参考文献：
  名称：

  Unsaturated Acyclic Analogs of 2'-Deoxyadenosine and Thymidine Containing Fluorine: Synthesis and Biological Activity

  摘要：

  The syntheses and biological activities of fluorobutynol 11 and (E)- and (Z)-fluorobutenols 8a,d and 9a,d are described. Alkylation of adenine with bromofluorobutyne 13a afforded intermediate 14 which was converted to fluorobutynol 11. Aldehyde 16a and (carbothoxyfluoromethyl)triphenylphosphonium bromide furnished (E)- and (Z)-fluorobutenoates 19a and 20a accompanied by regioisomer 21a. A similar reaction of compound 16d afforded Z- and E-esters 19d and 20d. Reduction of the mixture of 19a and 20a with DIBALH gave (E)- and (Z)-fluoroalkenols 8a and 9a. Similarly, the Z-ester 19d gave (Z)-fluoroalkenol 9d. Both 19d and 20d were reduced with NaBH4 to give (Z)- and (E)-fluoroalkenols 9d and 8d. Hydrogenation of 19a and 20a afforded fluoro ester 23. A similar reduction of 8a and 9a led to fluoro alcohol 24 and the defluorinated product 25 which were separated by chromatography on a Bio-Rad AG 1-X2 (OH-) column. (Z)-Fluorobutenol 9a is a substrate for adenosine deaminase, whereas the E-isomer 8a is inert toward the enzyme. By contrast, analogue 8a inhibited the replication and cytopathic effect of HN-1 in ATH8 cells with an IC50 Of approximately 100 mu M, but the Z-isomer 9a was inactive. This effect was accompanied by 36% cytotoxicity at 100 mu M. Compounds 11 and 8d inhibited the growth of murine leukemia L1210 culture with IC50 = 89 and 60 mu M, respectively.

  DOI：

  10.1021/jm00006a004

文献信息

• Unsaturated Acyclic Analogs of 2'-Deoxyadenosine and Thymidine Containing Fluorine: Synthesis and Biological Activity
  作者：Ze-Qi Xu、Yao-Ling Qiu、Sudhichai Chokekijchai、Hiroaki Mitsuya、Jiri Zemlicka

  DOI：10.1021/jm00006a004

  日期：1995.3

  The syntheses and biological activities of fluorobutynol 11 and (E)- and (Z)-fluorobutenols 8a,d and 9a,d are described. Alkylation of adenine with bromofluorobutyne 13a afforded intermediate 14 which was converted to fluorobutynol 11. Aldehyde 16a and (carbothoxyfluoromethyl)triphenylphosphonium bromide furnished (E)- and (Z)-fluorobutenoates 19a and 20a accompanied by regioisomer 21a. A similar reaction of compound 16d afforded Z- and E-esters 19d and 20d. Reduction of the mixture of 19a and 20a with DIBALH gave (E)- and (Z)-fluoroalkenols 8a and 9a. Similarly, the Z-ester 19d gave (Z)-fluoroalkenol 9d. Both 19d and 20d were reduced with NaBH4 to give (Z)- and (E)-fluoroalkenols 9d and 8d. Hydrogenation of 19a and 20a afforded fluoro ester 23. A similar reduction of 8a and 9a led to fluoro alcohol 24 and the defluorinated product 25 which were separated by chromatography on a Bio-Rad AG 1-X2 (OH-) column. (Z)-Fluorobutenol 9a is a substrate for adenosine deaminase, whereas the E-isomer 8a is inert toward the enzyme. By contrast, analogue 8a inhibited the replication and cytopathic effect of HN-1 in ATH8 cells with an IC50 Of approximately 100 mu M, but the Z-isomer 9a was inactive. This effect was accompanied by 36% cytotoxicity at 100 mu M. Compounds 11 and 8d inhibited the growth of murine leukemia L1210 culture with IC50 = 89 and 60 mu M, respectively.