(2S,3R,4R,5S)-3-(benzyloxy)-4-hydroxy-5-methoxy-4-methyltetrahydrofuran-2-carbaldehyde | 1608456-11-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,3R,4R,5S)-3-(benzyloxy)-4-hydroxy-5-methoxy-4-methyltetrahydrofuran-2-carbaldehyde
• 英文别名: (2S,3R,4R,5S)-4-hydroxy-5-methoxy-4-methyl-3-phenylmethoxyoxolane-2-carbaldehyde
• CAS: 1608456-11-6
• 化学式: C₁₄H₁₈O₅
• 分子量: 266.294
• InChiKey: VTLHNHORADLEMY-YIYPIFLZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,3R,4R,5S)-3-(benzyloxy)-4-hydroxy-5-methoxy-4-methyltetrahydrofuran-2-carbaldehyde 在 吡啶 、 硫酸 、 水 、 溶剂黄146 、 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 210.0h， 生成 (2R,3R,4R)-4-(benzyloxy)-3-methyl-5,5-bis(((methylsulfonyl)oxy)methyl)tetrahydrofuran-2,3-diyldiacetate
  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：

  (R)-1-((2R,3R,4R,5S)-3-(benzyloxy)-4-hydroxy-5-methoxy-4-methyltetrahydrofuran-2-yl)ethane-1,2-diol 在 sodium periodate 作用下， 以 水 为溶剂， 反应 0.5h， 以91%的产率得到(2S,3R,4R,5S)-3-(benzyloxy)-4-hydroxy-5-methoxy-4-methyltetrahydrofuran-2-carbaldehyde
  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

文献信息

• 2',4'-BRIDGED NUCLEOSIDES FOR HCV INFECTION
  申请人：Idenix Pharmaceuticals LLC

  公开号：EP2909222B1

  公开（公告）日：2021-05-26