(1'R,2'S,3'R)-1-[2,3-(isopropylidenedioxy)-4-(tert-butoxymethyl)-4-cyclopenten-1-yl]-5-fluorouracil | 377748-94-2

• 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: (1'R,2'S,3'R)-1-[2,3-(isopropylidenedioxy)-4-(tert-butoxymethyl)-4-cyclopenten-1-yl]-5-fluorouracil
• CAS: 377748-94-2
• 化学式: C₁₇H₂₃FN₂O₅
• 分子量: 354.378
• InChiKey: UYGBKLUOMJIPJV-UPJWGTAASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.49
• 重原子数：
  25.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  82.55
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (1'R,2'S,3'R)-1-[2,3-(isopropylidenedioxy)-4-(tert-butoxymethyl)-4-cyclopenten-1-yl]-5-fluorouracil 在 4-二甲氨基吡啶 、 三乙胺 、 三氟乙酸 作用下， 以 乙腈 为溶剂， 反应 34.0h， 生成 (1'R,2'S,3'R)-1-[2,3-dihydroxy-4-hydroxymethyl-4-cyclopenten-1-yl]-5-fluorocytosine
  参考文献：
  名称：

  Enantiomeric Synthesis of d- and l-Cyclopentenyl Nucleosides and Their Antiviral Activity Against HIV and West Nile Virus

  摘要：

  Enantiomeric synthesis Of D- and L-cyclopentenyl nucleosides and their antiviral activity against HIV and West Nile virus are described. The key intermediate (-)- and (+)-cyclopentenyl alcohols (7 and 15) were prepared from D-gamma -ribonolactone and D-ribose, respectively. Coupling of 7 with appropriately blocked purine and pyrimidine bases via the Mitsunobu reaction followed by deprotection afforded the target L-(+)-cyclopentenyl nucleosides (24-28, 31, 33, and 36). D-(-)Cyclopentenyl nucleosides (1, 40, 43, and 52-56) were also prepared by a similar procedure for L-isomers from 15. The synthesized compounds were evaluated for their antiviral activity against two RNA viruses: HIV and West Nile virus. Among the synthesized D-(-)-nucleosides, adenine (1, neplanocin A), cytosine (55, CPE-C), and 5-fluorocytosine (56) analogues exhibited moderate to potent anti-HIV activity (EC50 0.1, 0.06, and 5.34 muM, respectively) with significant cytotoxicity in PBM, Vero, and CEM cells. Also, cytosine (55) and 5-fluorocytosine (56) analogues exhibited the most potent anti-West Nile virus activity (EC50 0.2-3.0 and 15-20 muM, respectively). Among L-(+)-nucleosides, only the cytosine (27) analogue exhibited weak anti-HIV activity (EC50 58.9 muM).

  DOI：

  10.1021/jm010256v
• 作为产物：
  描述：

  甲基叔丁基醚 在 4-二甲氨基吡啶 、 双(乙腈)氯化钯(II) 、 potassium tert-butylate 、 氨 、 仲丁基锂 、 三乙胺 、 三苯基膦 、 对苯醌 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 74.5h， 生成 (1'R,2'S,3'R)-1-[2,3-(isopropylidenedioxy)-4-(tert-butoxymethyl)-4-cyclopenten-1-yl]-5-fluorouracil
  参考文献：
  名称：

  Enantiomeric Synthesis of d- and l-Cyclopentenyl Nucleosides and Their Antiviral Activity Against HIV and West Nile Virus

  摘要：

  Enantiomeric synthesis Of D- and L-cyclopentenyl nucleosides and their antiviral activity against HIV and West Nile virus are described. The key intermediate (-)- and (+)-cyclopentenyl alcohols (7 and 15) were prepared from D-gamma -ribonolactone and D-ribose, respectively. Coupling of 7 with appropriately blocked purine and pyrimidine bases via the Mitsunobu reaction followed by deprotection afforded the target L-(+)-cyclopentenyl nucleosides (24-28, 31, 33, and 36). D-(-)Cyclopentenyl nucleosides (1, 40, 43, and 52-56) were also prepared by a similar procedure for L-isomers from 15. The synthesized compounds were evaluated for their antiviral activity against two RNA viruses: HIV and West Nile virus. Among the synthesized D-(-)-nucleosides, adenine (1, neplanocin A), cytosine (55, CPE-C), and 5-fluorocytosine (56) analogues exhibited moderate to potent anti-HIV activity (EC50 0.1, 0.06, and 5.34 muM, respectively) with significant cytotoxicity in PBM, Vero, and CEM cells. Also, cytosine (55) and 5-fluorocytosine (56) analogues exhibited the most potent anti-West Nile virus activity (EC50 0.2-3.0 and 15-20 muM, respectively). Among L-(+)-nucleosides, only the cytosine (27) analogue exhibited weak anti-HIV activity (EC50 58.9 muM).

  DOI：

  10.1021/jm010256v