tert-butyl-[[(1R,5S,8R,10S,11R)-5-ethoxy-3,3-dioxo-10-phenylsulfanyl-2,9-dioxa-3lambda6-thia-6-azatricyclo[6.3.0.01,5]undecan-11-yl]oxy]-dimethylsilane | 1375389-81-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃吡咯
• 英文名称: tert-butyl-[[(1R,5S,8R,10S,11R)-5-ethoxy-3,3-dioxo-10-phenylsulfanyl-2,9-dioxa-3lambda6-thia-6-azatricyclo[6.3.0.01,5]undecan-11-yl]oxy]-dimethylsilane
• 英文别名: tert-butyl-[[(1R,5S,8R,10S,11R)-5-ethoxy-3,3-dioxo-10-phenylsulfanyl-2,9-dioxa-3λ6-thia-6-azatricyclo[6.3.0.01,5]undecan-11-yl]oxy]-dimethylsilane
• CAS: 1375389-81-3
• 化学式: C₂₁H₃₃NO₆S₂Si
• 分子量: 487.714
• InChiKey: WCBZNZQVMCICGA-MGSPEMMDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.33
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (3R,4R,5R)-4-cyano-4-((methylsulfonyl)oxy)-5-((tosyloxy)methyl)tetrahydrofuran-2,3-diyl diacetate 在 4-二甲氨基吡啶 、 三氟化硼乙醚 、 氨 、 potassium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 1.17h， 生成 tert-butyl-[[(1R,5S,8R,10S,11R)-5-ethoxy-3,3-dioxo-10-phenylsulfanyl-2,9-dioxa-3lambda6-thia-6-azatricyclo[6.3.0.01,5]undecan-11-yl]oxy]-dimethylsilane
  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 Finally, the thymine of the prototype compound has been replaced by N-3-methylthymine, uracil or thiophenyl.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.