5',N⁴''-cyclo{1-[2'-O-(tert-butyldimethylsilyl)-5'-deoxy-β-D-ribofuranosyl]thymine}-3'-spiro-5''-(4''-amino-4''S-neopentyloxy-1'',2''-oxathiolane-2'',2''-dioxide)

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5',N⁴''-cyclo{1-[2'-O-(tert-butyldimethylsilyl)-5'-deoxy-β-D-ribofuranosyl]thymine}-3'-spiro-5''-(4''-amino-4''S-neopentyloxy-1'',2''-oxathiolane-2'',2''-dioxide)
• 英文别名: 1-[(1R,5S,8R,10R,11R)-11-[tert-butyl(dimethyl)silyl]oxy-5-(2,2-dimethylpropoxy)-3,3-dioxo-2,9-dioxa-3lambda6-thia-6-azatricyclo[6.3.0.01,5]undecan-10-yl]-5-methylpyrimidine-2,4-dione；1-[(1R,5S,8R,10R,11R)-11-[tert-butyl(dimethyl)silyl]oxy-5-(2,2-dimethylpropoxy)-3,3-dioxo-2,9-dioxa-3λ6-thia-6-azatricyclo[6.3.0.01,5]undecan-10-yl]-5-methylpyrimidine-2,4-dione
• 化学式: C₂₃H₃₉N₃O₈SSi
• 分子量: 545.729
• InChiKey: HISSMQZGKYNQOB-QRTXUITFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.59
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  141
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5',N⁴''-cyclo{1-[2'-O-(tert-butyldimethylsilyl)-5'-deoxy-β-D-ribofuranosyl]thymine}-3'-spiro-5''-(4''-amino-4''S-neopentyloxy-1'',2''-oxathiolane-2'',2''-dioxide) 在 甲醇 、 氟化铵 作用下， 生成 1-[(1S,5S,8R,10R,11R)-5-(2,2-dimethylpropoxy)-11-hydroxy-3,3-dioxo-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 Finally, the thymine of the prototype compound has been replaced by N-3-methylthymine, uracil or thiophenyl.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
• 作为产物：
  描述：

  Toluene-4-sulfonic acid (5R,6R,8R,9R)-4-amino-9-(tert-butyl-dimethyl-silanyloxy)-8-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-2,2-dioxo-1,7-dioxa-2λ⁶-thia-spiro[4.4]non-3-en-6-ylmethyl ester 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 6.0h， 生成 5',N⁴''-cyclo{1-[2'-O-(tert-butyldimethylsilyl)-5'-deoxy-β-D-ribofuranosyl]thymine}-3'-spiro-5''-(4''-amino-4''S-neopentyloxy-1'',2''-oxathiolane-2'',2''-dioxide)
  参考文献：
  名称：

  TSAO-T衍生的常见环烯胺与亲核试剂的反应合成新型的双环，三环和四环核苷

  摘要：

  我们在这里报告了一种有效的区域和立体选择性合成新的多环核苷的方法，该方法使用一种常见的环烯胺（7）作为起始原料。实际上，7的反应很容易通过5'- O -Tosyl TSAO-T在碱性非亲核条件下（碳酸钾）与不同种类的亲核试剂反应而制备，例如，基于氮，氧，硫和碳的亲核试剂，或提供的氨基酸，具有总的区域和立体选择性，新的双，三和四环核苷。这种直截了当的途径代表了这些化合物的原始且明确的区域和立体选择性途径。这些多环核苷中的某些可能是第二系列反应的有用中间体，这些反应可能导致结构上新的核苷的产生。

  DOI：

  10.1021/jo048706p

文献信息

• Synthesis of Novel Bi-, Tri-, and Tetracyclic Nucleosides by Reaction of a Common Cyclic Enamine Derived from TSAO-T with Nucleophiles
  作者：María-Cruz Bonache、Cristina Chamorro、Alessandra Cordeiro、María-José Camarasa、María-Luisa Jimeno、Ana San-Félix

  DOI：10.1021/jo048706p

  日期：2004.12.1

  nucleophiles, or with amino acids afforded, with total regio- and stereoselectivity, new bi-, tri-, and tetracyclic nucleosides. This straighforward route represents an original and unambiguously regio- and stereoselective pathway to these compounds. Some of these polycyclic nucleosides may be useful intermediates for a second series of reactions that may lead to the generation of structurally new nucleosides

  我们在这里报告了一种有效的区域和立体选择性合成新的多环核苷的方法，该方法使用一种常见的环烯胺（7）作为起始原料。实际上，7的反应很容易通过5'- O -Tosyl TSAO-T在碱性非亲核条件下（碳酸钾）与不同种类的亲核试剂反应而制备，例如，基于氮，氧，硫和碳的亲核试剂，或提供的氨基酸，具有总的区域和立体选择性，新的双，三和四环核苷。这种直截了当的途径代表了这些化合物的原始且明确的区域和立体选择性途径。这些多环核苷中的某些可能是第二系列反应的有用中间体，这些反应可能导致结构上新的核苷的产生。
• 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.