(5aR,7S,8R,8aR)-8-((tert-butyldimethylsilyl)oxy)-7-(phenylthio)-5,5a,7,8-tetrahydro-4H-furo[3,2-c][1,2]oxathiolo[4,5-b]pyrrole 2,2-dioxide | 1375389-80-2

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: (5aR,7S,8R,8aR)-8-((tert-butyldimethylsilyl)oxy)-7-(phenylthio)-5,5a,7,8-tetrahydro-4H-furo[3,2-c][1,2]oxathiolo[4,5-b]pyrrole 2,2-dioxide
• CAS: 1375389-80-2
• 化学式: C₁₉H₂₇NO₅S₂Si
• 分子量: 441.645
• InChiKey: OUNKYFUNGKZZFL-VUHPKUFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.44
• 重原子数：
  28.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  73.86
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  乙醇 、 (5aR,7S,8R,8aR)-8-((tert-butyldimethylsilyl)oxy)-7-(phenylthio)-5,5a,7,8-tetrahydro-4H-furo[3,2-c][1,2]oxathiolo[4,5-b]pyrrole 2,2-dioxide 以79%的产率得到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 Finally, the thymine of the prototype compound has been replaced by N-3-methylthymine, uracil or thiophenyl.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
• 作为产物：
  描述：

  (2S,3R,4R,5R)-4-cyano-4-((methylsulfonyl)oxy)-2-(phenylthio)-5-((tosyloxy)methyl)tetrahydrofuran-3-yl acetate 在 4-二甲氨基吡啶 、 氨 、 potassium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 1.17h， 生成 (5aR,7S,8R,8aR)-8-((tert-butyldimethylsilyl)oxy)-7-(phenylthio)-5,5a,7,8-tetrahydro-4H-furo[3,2-c][1,2]oxathiolo[4,5-b]pyrrole 2,2-dioxide
  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