1-[(1R,5S,8R,10R,11R)-11-[tert-butyl(dimethyl)silyl]oxy-3,3-dioxo-5-prop-2-ynoxy-2,9-dioxa-3lambda6-thia-6-azatricyclo[6.3.0.01,5]undecan-10-yl]-5-methylpyrimidine-2,4-dione | 1375389-47-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[(1R,5S,8R,10R,11R)-11-[tert-butyl(dimethyl)silyl]oxy-3,3-dioxo-5-prop-2-ynoxy-2,9-dioxa-3lambda6-thia-6-azatricyclo[6.3.0.01,5]undecan-10-yl]-5-methylpyrimidine-2,4-dione
• 英文别名: 1-[(1R,5S,8R,10R,11R)-11-[tert-butyl(dimethyl)silyl]oxy-3,3-dioxo-5-prop-2-ynoxy-2,9-dioxa-3λ6-thia-6-azatricyclo[6.3.0.01,5]undecan-10-yl]-5-methylpyrimidine-2,4-dione
• CAS: 1375389-47-1
• 化学式: C₂₁H₃₁N₃O₈SSi
• 分子量: 513.644
• InChiKey: KLAOOVMVJADZFK-GAWMMQFTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.18
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  141
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  5',N⁴''-cyclo{1-[2'-O-(tert-butyldimethylsilyl)-5'-deoxy-β-D-ribofuranosyl]thymine}-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide) 、 2-丙炔-1-醇 以 乙腈 为溶剂， 以76%的产率得到1-[(1R,5S,8R,10R,11R)-11-[tert-butyl(dimethyl)silyl]oxy-3,3-dioxo-5-prop-2-ynoxy-2,9-dioxa-3lambda6-thia-6-azatricyclo[6.3.0.01,5]undecan-10-yl]-5-methylpyrimidine-2,4-dione
  参考文献：
  名称：

  Selective inhibition of Human Immunodeficiency Virus type 1 (HIV-1) by a novel family of tricyclic nucleosides

  摘要：

  Nucleoside 1, with an unusual tricyclic carbohydrate moiety, specifically inhibits HIV-1 replication while being inactive against HIV-2 or other (retro) viruses. In an attempt to increase the inhibitory efficacy against HIV-1, and to further explore the structural features required for anti-HIV-1 activity, different types of modifications have been carried out on this prototype compound. These include substitution of the ethoxy group at the C-4" position by alkoxy groups of different length, branching, conformational freedom or functionalization. In addition, the 4"-ethoxy group has been removed or substituted by other functional groups. The role of the tert-butyldimethylsilyl (TBDMS) group at the 2' position has also been studied by preparing the corresponding 2'-deprotected derivative or by replacing it by other silyl (tert-hexyldimethylsilyl) or acyl (acetyl) moieties. Finally, the thymine of the prototype compound has been replaced by N-3-methylthymine, uracil or thiophenyl. Some of these compounds were endowed with a 6- to 7-fold higher selectivity than the prototype 1. The tricyclic nucleosides here described represent a novel type of selective anti HIV-1 inhibitors, targeted at the HIV-1-encoded reverse transcriptase. (C) 2011 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.antiviral.2011.05.002

文献信息

• Selective inhibition of Human Immunodeficiency Virus type 1 (HIV-1) by a novel family of tricyclic nucleosides
  作者：María-Cruz Bonache、Alessandra Cordeiro、Ernesto Quesada、Els Vanstreels、Dirk Daelemans、María-José Camarasa、Jan Balzarini、Ana San-Félix

  DOI：10.1016/j.antiviral.2011.05.002

  日期：2011.10

  Nucleoside 1, with an unusual tricyclic carbohydrate moiety, specifically inhibits HIV-1 replication while being inactive against HIV-2 or other (retro) viruses. In an attempt to increase the inhibitory efficacy against HIV-1, and to further explore the structural features required for anti-HIV-1 activity, different types of modifications have been carried out on this prototype compound. These include substitution of the ethoxy group at the C-4" position by alkoxy groups of different length, branching, conformational freedom or functionalization. In addition, the 4"-ethoxy group has been removed or substituted by other functional groups. The role of the tert-butyldimethylsilyl (TBDMS) group at the 2' position has also been studied by preparing the corresponding 2'-deprotected derivative or by replacing it by other silyl (tert-hexyldimethylsilyl) or acyl (acetyl) moieties. Finally, the thymine of the prototype compound has been replaced by N-3-methylthymine, uracil or thiophenyl. Some of these compounds were endowed with a 6- to 7-fold higher selectivity than the prototype 1. The tricyclic nucleosides here described represent a novel type of selective anti HIV-1 inhibitors, targeted at the HIV-1-encoded reverse transcriptase. (C) 2011 Elsevier B.V. All rights reserved.