((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 benzoate | 1094603-23-2

• 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 benzoate
• 英文别名: (1S,3R,4R,7S)-1-benzoyloxymethyl-7-benzyloxy-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 benzoate
• CAS: 1094603-23-2
• 化学式: C₂₄H₂₂N₂O₇
• 分子量: 450.448
• InChiKey: SNVWHPVGWFNEKF-OOICKAIWSA-N

物化性质

• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  7

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 benzoate 在 甲醇 、 palladium 10% on activated carbon 、 氢气 、 sodium methylate 、 溶剂黄146 作用下， 反应 21.0h， 生成 1-(2’-O,4-C-甲桥-BETA-D-呋喃核糖基)尿苷
  参考文献：
  名称：

  作为 MraY 抑制剂的 LNA/BNA 型 5'-O-氨基核糖苷尿苷的设计、合成和构象-活性关系分析

  摘要：

  了解和控制药物化学中的生物活性构象非常重要。Muraymycins 和 caprazamycins 是 MraY 的强抑制剂，是具有新作用方式的有前途的抗菌剂。着眼于这些天然产物的尿苷部分的糖褶皱和二面角 φ，设计了 LNA/BNA 型 5'-O-氨基核糖基尿苷类似物，其核糖部分的褶皱完全限于N型。合成为简化的 MraY 抑制剂。进一步详细研究了它们的构象-活性关系。本研究中研究的构象-活性关系分析可以作为简化和合理设计 MraY 抑制性核苷天然产物的一般指南。

  DOI：

  10.1016/j.bmc.2022.116744
• 作为产物：
  描述：

  3-O-benzyl-1,2-O-isopropylidene-α-D-ribo-pentodialdofuranose 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 、 1,4-二氧六环 、 甲醇 、 水 、 溶剂黄146 、 二甲基亚砜 、 乙腈 为溶剂， 反应 155.0h， 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 benzoate
  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.
• Design, synthesis and conformation-activity relationship analysis of LNA/BNA-type 5′-O-aminoribosyluridine as MraY inhibitors
  作者：Shintaro Kusaka、Kazuki Yamamoto、Motoko Shinohara、Yusuke Minato、Satoshi Ichikawa

  DOI：10.1016/j.bmc.2022.116744

  日期：2022.7

  the uridine moiety of these natural products, LNA/BNA-type 5′-O-aminoribosyluridine analogues, whose puckering of the ribose moiety are completely restricted to the N-type, were designed and synthesized as simplified MraY inhibitors. Their conformation-activity relationship was further investigated in details. The conformation-activity relationship analysis investigated in this study could be a general

  了解和控制药物化学中的生物活性构象非常重要。Muraymycins 和 caprazamycins 是 MraY 的强抑制剂，是具有新作用方式的有前途的抗菌剂。着眼于这些天然产物的尿苷部分的糖褶皱和二面角 φ，设计了 LNA/BNA 型 5'-O-氨基核糖基尿苷类似物，其核糖部分的褶皱完全限于N型。合成为简化的 MraY 抑制剂。进一步详细研究了它们的构象-活性关系。本研究中研究的构象-活性关系分析可以作为简化和合理设计 MraY 抑制性核苷天然产物的一般指南。