diisopropyl {[(1R)-2-[(4-amino-1,3,5-triazin-2-yl)oxy]-1-(hydroxymethyl)ethoxy]methyl}-phosphonate | 1207842-50-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: diisopropyl {[(1R)-2-[(4-amino-1,3,5-triazin-2-yl)oxy]-1-(hydroxymethyl)ethoxy]methyl}-phosphonate
• CAS: 1207842-50-9
• 化学式: C₁₃H₂₅N₄O₆P
• 分子量: 364.338
• InChiKey: GDVVNZACWALWAJ-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.21
• 重原子数：
  24.0
• 可旋转键数：
  11.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  138.91
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为产物：
  描述：

  5-氮杂胞嘧啶 、 (R)-2-[(diisopropoxyphosphoryl)methoxy]-3-hydroxypropyl p-toluenesulfonate 在 sodium methylate 、 caesium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以62%的产率得到1-[(2S)-2-(diisopropoxyphosphoryl)methoxy-3-hydroxypropyl]-5-azacytosine
  参考文献：
  名称：

  Acyclic nucleoside phosphonates with 5-azacytosine base moiety substituted in C-6 position

  摘要：

  Two methods for preparation of 6-substituted derivatives of anti DNA-viral agent 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine (HPMP-5-azaC) were developed: (1) ammonia mediated ring-opening reaction of diisopropyl esters of HPMP-5-azaC (4) to carbamoylguanidine derivatives followed by ring-closure reaction with orthoesters and (2) condensation reaction of 6-substituted 5-azacytosines with diisopropyl (1S)-[2-hydroxy-1-tosyloxymethyl)ethoxy]methylphosphonate (15). Deprotection of diisopropyl esters to free phosphonic acids was performed with bromotrimethylsilane in acetonitrile followed by hydrolysis. In contrast to parent compound HPMP-5-azaC, a substantial decrease of antiviral activity in case of 6-substituted analogues occurred. Surprisingly, N-3 isomer of 6-methyl-HPMP-5-azaC in the form of isopropyl ester revealed activity against RNA viruses (Sindbis virus). (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.10.044