tetradecanoyl 3'-azido-3'-deoxy-5'-thymidylphosphate

• 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: tetradecanoyl 3'-azido-3'-deoxy-5'-thymidylphosphate
• 英文别名: Myr-AZTMP；[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] tetradecanoate
• 化学式: C₂₄H₄₀N₅O₈P
• 分子量: 557.584
• InChiKey: UKGSSADQICBWMJ-PWRODBHTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  38
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  146
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  tetradecanoyl 3'-azido-3'-deoxy-5'-thymidylphosphate 在 水 、 乙酸–三乙胺 作用下， 生成 (3'-azido-3'-deoxy)thymidine monophosphate sodium salt
  参考文献：
  名称：

  Potential Lipophilic Nucleotide Prodrugs:  Synthesis, Hydrolysis, and Antiretroviral Activity of AZT and d4T Acyl Nucleotides

  摘要：

  Three general methods for the synthesis of acyl nucleotides (mono-, di-, and triphosphates) have been developed and applied to different HIV inhibitors. These new types of compounds, where a fatty acid moiety is linked to the nucleotide phosphate chain by an acyl phosphate bond, were designed as lipophilic prodrugs of HIV inhibitors metabolites. Acyl nucleoside monophosphates la,b were prepared by acylation of the corresponding nucleoside monophosphates. Acyl nucleoside diphosphates 2a-c and 3a,b were synthesized directly from the free nucleosides using DCC activation of acyl pyrophosphates. Acyl nucleoside triphosphates 4a-c and 5a were obtained using phosphoromorpholidate chemistry and acyl pyrophosphates as nucleophiles. Hydrolysis of acyl nucleotides liberated the corresponding nucleotides by selective cleavage of the acyl phosphate bond, with half lives ranging from 51 to 185 h at 37 degrees C in triethylammonium acetate buffer pH 7.0. Their antiretroviral activity, measured by the inhibition of cytopathogenicity and reverse transcriptase activity in the cultures supernatants, did not reveal any differences between an acyl nucleotide and its corresponding nucleotide. These results are explained in term of rapid aminolysis of the acyl phosphate bond in culture media.

  DOI：

  10.1021/jo951354p
• 作为产物：
  描述：

  肉豆蔻酸 、 (3'-azido-3'-deoxy)thymidine monophosphate sodium salt 在 4-二甲氨基吡啶 、 Dowex AG 50WX₈ 200 (NBu₄⁺) 、 N,N'-二环己基碳二亚胺 作用下， 生成 tetradecanoyl 3'-azido-3'-deoxy-5'-thymidylphosphate
  参考文献：
  名称：

  Potential Lipophilic Nucleotide Prodrugs:  Synthesis, Hydrolysis, and Antiretroviral Activity of AZT and d4T Acyl Nucleotides

  摘要：

  Three general methods for the synthesis of acyl nucleotides (mono-, di-, and triphosphates) have been developed and applied to different HIV inhibitors. These new types of compounds, where a fatty acid moiety is linked to the nucleotide phosphate chain by an acyl phosphate bond, were designed as lipophilic prodrugs of HIV inhibitors metabolites. Acyl nucleoside monophosphates la,b were prepared by acylation of the corresponding nucleoside monophosphates. Acyl nucleoside diphosphates 2a-c and 3a,b were synthesized directly from the free nucleosides using DCC activation of acyl pyrophosphates. Acyl nucleoside triphosphates 4a-c and 5a were obtained using phosphoromorpholidate chemistry and acyl pyrophosphates as nucleophiles. Hydrolysis of acyl nucleotides liberated the corresponding nucleotides by selective cleavage of the acyl phosphate bond, with half lives ranging from 51 to 185 h at 37 degrees C in triethylammonium acetate buffer pH 7.0. Their antiretroviral activity, measured by the inhibition of cytopathogenicity and reverse transcriptase activity in the cultures supernatants, did not reveal any differences between an acyl nucleotide and its corresponding nucleotide. These results are explained in term of rapid aminolysis of the acyl phosphate bond in culture media.

  DOI：

  10.1021/jo951354p