(Z)-4-(thymin-N¹-yl)-2-fluoro-2-buten-1-ol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (Z)-4-(thymin-N¹-yl)-2-fluoro-2-buten-1-ol
• 英文别名: 1-[(Z)-3-fluoro-4-hydroxybut-2-enyl]-5-methylpyrimidine-2,4-dione
• 化学式: C₉H₁₁FN₂O₃
• 分子量: 214.196
• InChiKey: JHXWUMRPEAVDHB-UQCOIBPSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetaldehyde 在 sodium tetrahydroborate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.5h， 生成 (Z)-4-(thymin-N¹-yl)-2-fluoro-2-buten-1-ol
  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