(2R,3R,4S,5R)-2-(2-amino-6-chloro-9H-purin-9-yl)-4-(benzyloxy)-5-((benzyloxy)methyl)-5-(2-(tosyloxy)ethyl)tetrahydrofuran-3-yl acetate | 1610605-74-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: (2R,3R,4S,5R)-2-(2-amino-6-chloro-9H-purin-9-yl)-4-(benzyloxy)-5-((benzyloxy)methyl)-5-(2-(tosyloxy)ethyl)tetrahydrofuran-3-yl acetate
• CAS: 1610605-74-7
• 化学式: C₃₅H₃₆ClN₅O₈S
• 分子量: 722.219
• InChiKey: VFQXKSCLIJWDPR-ACZXLBTNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.17
• 重原子数：
  50.0
• 可旋转键数：
  14.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  166.98
• 氢给体数：
  1.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  (2R,3R,4S,5R)-2-(2-amino-6-chloro-9H-purin-9-yl)-4-(benzyloxy)-5-((benzyloxy)methyl)-5-(2-(tosyloxy)ethyl)tetrahydrofuran-3-yl acetate 在 sodium hydride 、 3-羟基丙腈 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 72.0h， 以2 g的产率得到2-amino-9-((1R,5R,7R,8S)-8-(benzyloxy)-5-((benzyloxy)methyl)-2,6-dioxabicyclo[3.2.1]octan-7-yl)-1H-purin-6(9H)-one
  参考文献：
  名称：

  Synthesis of 2′-O,4′-C-alkylene-bridged ribonucleosides and their evaluation as inhibitors of HCV NS5B polymerase

  摘要：

  The synthesis of 2'-O,4'-C-methylene-bridged bicyclic guanine ribonucleosides bearing 2'-C-methyl or 5'C-methyl modifications is described. Key to the successful installation of the methyl functionality in both cases was the use of a one-pot oxidation-Grignard procedure to avoid formation of the respective unreactive hydrates prior to alkylation. The 2'-C-methyl- and 5'-C-methyl-modified bicyclic guanosines were evaluated, along with the known uracil-, cytosine-, adenine-, guanine-LNA and guanine-ENA nucleosides, as potential antiviral agents and found to be inactive in the hepatitis C virus (HCV) cell-based replicon assay. Examination of the corresponding nucleoside triphosphates, however, against the purified HCV NS5B polymerase indicated that LNA-G and 2'-C-methyl-LNA-G are potent inhibitors of both 1b wild type and S282T mutant enzymes in vitro. Activity was further demonstrated for the LNA-G-triphosphate against HCV NS5B polymerase genotypes 1a, 2a, 3a and 4a. A phosphorylation by-pass prodrug strategy may be required to promote anti-HCV activity in the replicon assay. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.050
• 作为产物：
  描述：

  (3aR,5R,6S,6aR)-6-(benzyloxy)-5-((benzyloxy)methyl)-2,2-dimethyl-5-vinyltetrahydrofuro[2,3-d][1,3]dioxole 在 4-二甲氨基吡啶 、 9-borabicyclo[3.3.1]nonane dimer 、 N,O-双三甲硅基乙酰胺 、 硫酸 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 溶剂黄146 、 1,2-二氯乙烷 为溶剂， 反应 42.0h， 生成 (2R,3R,4S,5R)-2-(2-amino-6-chloro-9H-purin-9-yl)-4-(benzyloxy)-5-((benzyloxy)methyl)-5-(2-(tosyloxy)ethyl)tetrahydrofuran-3-yl acetate
  参考文献：
  名称：

  Synthesis of 2′-O,4′-C-alkylene-bridged ribonucleosides and their evaluation as inhibitors of HCV NS5B polymerase

  摘要：

  The synthesis of 2'-O,4'-C-methylene-bridged bicyclic guanine ribonucleosides bearing 2'-C-methyl or 5'C-methyl modifications is described. Key to the successful installation of the methyl functionality in both cases was the use of a one-pot oxidation-Grignard procedure to avoid formation of the respective unreactive hydrates prior to alkylation. The 2'-C-methyl- and 5'-C-methyl-modified bicyclic guanosines were evaluated, along with the known uracil-, cytosine-, adenine-, guanine-LNA and guanine-ENA nucleosides, as potential antiviral agents and found to be inactive in the hepatitis C virus (HCV) cell-based replicon assay. Examination of the corresponding nucleoside triphosphates, however, against the purified HCV NS5B polymerase indicated that LNA-G and 2'-C-methyl-LNA-G are potent inhibitors of both 1b wild type and S282T mutant enzymes in vitro. Activity was further demonstrated for the LNA-G-triphosphate against HCV NS5B polymerase genotypes 1a, 2a, 3a and 4a. A phosphorylation by-pass prodrug strategy may be required to promote anti-HCV activity in the replicon assay. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.050