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 | 1620083-17-1

• 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: 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
• CAS: 1620083-17-1
• 化学式: C₁₅H₂₄N₃O₈P
• 分子量: 405.345
• InChiKey: KOVNMIBZHHHHOM-TUIIEMGHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.17
• 重原子数：
  27.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  155.36
• 氢给体数：
  3.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  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 在 三甲基溴硅烷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以8%的产率得到[(2R,3R,4S,5S,8S)-2-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3,4-dihydroxy-1,7-dioxaspiro[4.4]nonan-8-yl]phosphonic acid
  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 、 ammonium hydroxide 、 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 甲醇 、 二氯甲烷 、 水 、 甲苯 、 乙腈 为溶剂， 反应 72.08h， 生成 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