((1R,3R,4R,7S)-7-(benzyloxy)-3-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dioxabicyclo[2.2.1]heptan-1-yl)methyl methanesulfonate | 1094603-22-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ((1R,3R,4R,7S)-7-(benzyloxy)-3-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dioxabicyclo[2.2.1]heptan-1-yl)methyl methanesulfonate
• 英文别名: (1S,3R,4R,7S)-7-benzyloxy-1-methanesulfonoxymethyl-3-(uracil-1-yl)-2,5-dioxabicyclo[2.2.1]heptane；[(1R,3R,4R,7S)-3-(2,4-dioxopyrimidin-1-yl)-7-phenylmethoxy-2,5-dioxabicyclo[2.2.1]heptan-1-yl]methyl methanesulfonate
• CAS: 1094603-22-1
• 化学式: C₁₈H₂₀N₂O₈S
• 分子量: 424.431
• InChiKey: GZIHFWLUFRHQQD-KYHPRHEASA-N

物化性质

• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ((1R,3R,4R,7S)-7-(benzyloxy)-3-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dioxabicyclo[2.2.1]heptan-1-yl)methyl methanesulfonate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 3'-O-benzyl-2'-O,4'-C-methyleneuridine
  参考文献：
  名称：

  Chemoenzymatic Convergent Synthesis of 2′-O,4′-C-Methyleneribonucleosides

  摘要：

  Novozyme-435-catalyzed efficient regioselective acetylation of one of the two diastereotopic hydroxymethyl functions in 3-O-benzyl-4-C-hydroxymethyl-1,2-O-isopropylidene-alpha-D-ribofuranose has been achieved. The enzymatic methodology has been successfully utilized for convergent synthesis of bicyclic nucleosides (LNA monomers) T, U, A, and C. Further, it has been demonstrated that Novozyme-435 can be used for 10 cycles of the acylation reaction without losing selectivity and efficiency.

  DOI：

  10.1021/jo5008338
• 作为产物：
  描述：

  3-O-苄基-4-C-羟甲基-1,2-O-异亚丙基-ALPHA-D-呋喃核糖 在 吡啶 、 N,O-双三甲硅基乙酰胺 、 硫酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 溶剂黄146 、 乙腈 为溶剂， 反应 6.0h， 生成 ((1R,3R,4R,7S)-7-(benzyloxy)-3-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-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

文献信息

• Optimized synthesis of LNA uracil nucleosides
  作者：T. Santhosh Kumar、Pawan Kumar、Pawan K. Sharma、Patrick J. Hrdlicka

  DOI：10.1016/j.tetlet.2008.09.165

  日期：2008.12

  A short, very high yielding, and practical synthesis of LNA uracil diol 6 has been developed from the easily accessible glycosyl donor 1. The concluding O3′-debenzylation of 5 resulted in significant reduction of the uracil moiety with many typical debenzylation conditions, while catalytic transfer hydrogenation using Pd(OH)2/C and formic acid largely suppressed this undesired side reaction. Facile

  从容易获得的糖基供体1已经开发出短的，非常高的产率和实用的LNA尿嘧啶二醇6的合成。最后的O3'-脱苄基化反应5导致尿嘧啶部分在许多典型的脱苄基反应条件下显着降低，而使用Pd（OH）2 / C和甲酸的催化转移氢化反应则大大抑制了这种不良反应。轻松获得6个将允许全面探索基于RNA的LNA技术应用，包括聚合酶催化的LNA修饰RNA链的合成。
• Chemoenzymatic Convergent Synthesis of 2′-<i>O</i>,4′-<i>C</i>-Methyleneribonucleosides
  作者：Vivek K. Sharma、Manish Kumar、Carl E. Olsen、Ashok K. Prasad

  DOI：10.1021/jo5008338

  日期：2014.7.3

  Novozyme-435-catalyzed efficient regioselective acetylation of one of the two diastereotopic hydroxymethyl functions in 3-O-benzyl-4-C-hydroxymethyl-1,2-O-isopropylidene-alpha-D-ribofuranose has been achieved. The enzymatic methodology has been successfully utilized for convergent synthesis of bicyclic nucleosides (LNA monomers) T, U, A, and C. Further, it has been demonstrated that Novozyme-435 can be used for 10 cycles of the acylation reaction without losing selectivity and efficiency.
• Synthesis of 2′-O,4′-C-alkylene-bridged ribonucleosides and their evaluation as inhibitors of HCV NS5B polymerase
  作者：Christopher Chapron、Rebecca Glen、Massimiliano La Colla、Benjamin A. Mayes、Joseph F. McCarville、Stephen Moore、Adel Moussa、Ruhul Sarkar、Maria Seifer、Ilaria Serra、Alistair Stewart

  DOI：10.1016/j.bmcl.2014.04.050

  日期：2014.6

  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.