(2R,3R,4S,5S)-8-(diethoxyphosphoryl)-2-(4-acetamido-2-oxo-1,2-dihydropyrimidin-1-yl)-4-hydroxy-1,7-dioxaspiro[4.4]nonan-3-yl acetate | 1620083-16-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2R,3R,4S,5S)-8-(diethoxyphosphoryl)-2-(4-acetamido-2-oxo-1,2-dihydropyrimidin-1-yl)-4-hydroxy-1,7-dioxaspiro[4.4]nonan-3-yl acetate
• CAS: 1620083-16-0
• 化学式: C₁₉H₂₈N₃O₁₀P
• 分子量: 489.419
• InChiKey: IZFYFDJJVJKCEA-HZZYYBQKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.77
• 重原子数：
  33.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  164.51
• 氢给体数：
  2.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  (2R,3R,4S,5S)-8-(diethoxyphosphoryl)-2-(4-acetamido-2-oxo-1,2-dihydropyrimidin-1-yl)-4-hydroxy-1,7-dioxaspiro[4.4]nonan-3-yl acetate 在 ammonium hydroxide 作用下， 以 甲醇 为溶剂， 反应 1.5h， 以43%的产率得到diethyl [(2R,3R,4S,5S)-2-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3,4-dihydroxy-1,7-dioxaspiro[4.4]nonan-8-yl]phosphonate
  参考文献：
  名称：

  Syntheses of 4′-spirocyclic phosphono-nucleosides as potential inhibitors of hepatitis C virus NS5B polymerase

  摘要：

  To discover novel nucleosides as potential antiviral agents, 4'-spirocyclic phosphono-nucleosides were designed to mimic the monophosphate of R-1479, a known nucleoside inhibitor of HCV NS5B. Bypassing the first kinase step to nucleoside monophosphate is viewed as advantageous since this phosphorylation is often observed as the rate-limiting transformation to the active NTP for many nucleosides. Efficient synthetic routes were developed with a triphenylphosphine-iodine cyclization reaction as the key step to form the tetrahydrofuran 4'-spirocycle. The desired 4'-spirocyclic phosphono-cytidine analogs 12a, 12b, and 16 were prepared in 11 steps. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2014.06.029
• 作为产物：
  描述：

  diethyl 1-hydroxy-2-((3aR,5S,6S,6aR)-5-(hydroxymethyl)-2,2-dimethyl-6-(naphthalen-2-ylmethoxy)-dihydro-5H-furo[3,2-d][1,3]dioxol-5-yl)ethyl phosphonate 在 咪唑 、 N,O-双三甲硅基乙酰胺 、 硫酸 、 溶剂黄146 、 三苯基膦 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 、 水 、 甲苯 、 乙腈 为溶剂， 反应 70.58h， 生成 (2R,3R,4S,5S)-8-(diethoxyphosphoryl)-2-(4-acetamido-2-oxo-1,2-dihydropyrimidin-1-yl)-4-hydroxy-1,7-dioxaspiro[4.4]nonan-3-yl acetate
  参考文献：
  名称：

  Syntheses of 4′-spirocyclic phosphono-nucleosides as potential inhibitors of hepatitis C virus NS5B polymerase

  摘要：

  To discover novel nucleosides as potential antiviral agents, 4'-spirocyclic phosphono-nucleosides were designed to mimic the monophosphate of R-1479, a known nucleoside inhibitor of HCV NS5B. Bypassing the first kinase step to nucleoside monophosphate is viewed as advantageous since this phosphorylation is often observed as the rate-limiting transformation to the active NTP for many nucleosides. Efficient synthetic routes were developed with a triphenylphosphine-iodine cyclization reaction as the key step to form the tetrahydrofuran 4'-spirocycle. The desired 4'-spirocyclic phosphono-cytidine analogs 12a, 12b, and 16 were prepared in 11 steps. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2014.06.029