1-((5aR,7R,8R,8aR)-8-((tert-butyldimethylsilyl)oxy)-2,2-dioxido-5,5a,7,8-tetrahydro-4H-furo[3,2-c][1,2]oxathiolo[4,5-b]pyrrol-7-yl)pyrimidine-2,4(1H,3H)-dione | 1375389-75-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-((5aR,7R,8R,8aR)-8-((tert-butyldimethylsilyl)oxy)-2,2-dioxido-5,5a,7,8-tetrahydro-4H-furo[3,2-c][1,2]oxathiolo[4,5-b]pyrrol-7-yl)pyrimidine-2,4(1H,3H)-dione
• CAS: 1375389-75-5
• 化学式: C₁₇H₂₅N₃O₇SSi
• 分子量: 443.553
• InChiKey: VVCFOVNFVBOFMZ-ABYLEIOUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.37
• 重原子数：
  29.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  128.72
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  乙醇 、 1-((5aR,7R,8R,8aR)-8-((tert-butyldimethylsilyl)oxy)-2,2-dioxido-5,5a,7,8-tetrahydro-4H-furo[3,2-c][1,2]oxathiolo[4,5-b]pyrrol-7-yl)pyrimidine-2,4(1H,3H)-dione 以70%的产率得到1-[(1R,5S,8R,10R,11R)-11-[tert-butyl(dimethyl)silyl]oxy-5-ethoxy-3,3-dioxo-2,9-dioxa-3lambda6-thia-6-azatricyclo[6.3.0.01,5]undecan-10-yl]pyrimidine-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 Finally, the thymine of the prototype compound has been replaced by N-3-methylthymine, uracil or thiophenyl.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
• 作为产物：
  描述：

  ((2R,3R,4R,5R)-4-((tert-butyldimethylsilyl)oxy)-3-cyano-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3-((methylsulfonyl)oxy)tetrahydrofuran-2-yl)methyl 4-methylbenzenesulfonate 在 potassium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 5.0h， 生成 1-((5aR,7R,8R,8aR)-8-((tert-butyldimethylsilyl)oxy)-2,2-dioxido-5,5a,7,8-tetrahydro-4H-furo[3,2-c][1,2]oxathiolo[4,5-b]pyrrol-7-yl)pyrimidine-2,4(1H,3H)-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