(R)-1-((2R,3S,4R,5R)-3-(benzyloxy)-4-hydroxy-5-methoxytetrahydrofuran-2-yl)ethane-1,2-diyl dibenzoate | 1610605-76-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (R)-1-((2R,3S,4R,5R)-3-(benzyloxy)-4-hydroxy-5-methoxytetrahydrofuran-2-yl)ethane-1,2-diyl dibenzoate
• CAS: 1610605-76-9
• 化学式: C₂₈H₂₈O₈
• 分子量: 492.526
• InChiKey: AODAQLVWNLIMAN-MCGNWXOFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.39
• 重原子数：
  36.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  100.52
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (R)-1-((2R,3S,4R,5R)-3-(benzyloxy)-4-hydroxy-5-methoxytetrahydrofuran-2-yl)ethane-1,2-diyl dibenzoate 在 吡啶 、 sodium periodate 、 N,O-双三甲硅基乙酰胺 、 硫酸 、 氨 、 水 、 四氯化钛 、 sodium hydride 、 溶剂黄146 、 二甲基亚砜 、 3-羟基丙腈 、 三氟乙酸酐 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 1,2-二氯乙烷 、 mineral oil 为溶剂， 反应 253.25h， 生成 ((1R,3R,4R,7R)-3-(2-amino-6-oxo-1H-purin-9(6H)-yl)-7-(benzyloxy)-4-methyl-2,5-dioxabicyclo[2.2.1]heptan-1-yl)methyl methanesulfonate
  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：

  1,2:5,6-二异亚丙基-alpha-D-异呋喃糖 在 吡啶 、 盐酸 、 sodium hydride 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 水 、 乙腈 、 mineral oil 为溶剂， 反应 173.5h， 生成 (R)-1-((2R,3S,4R,5R)-3-(benzyloxy)-4-hydroxy-5-methoxytetrahydrofuran-2-yl)ethane-1,2-diyl dibenzoate
  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