3'-O-benzyl-2'-O,4'-C-methyleneuridine | 200435-91-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3'-O-benzyl-2'-O,4'-C-methyleneuridine
• 英文别名: (1S,3R,4R,7S)-7-benzyloxy-1-hydroxymethyl-3-(uracil-1-yl)-2,5-dioxabicyclo[2.2.1]heptane；1-((1S,3R,4R,7S)-7-(benzyloxy)-1-(hydroxymethyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl)pyrimidine-2,4(1H,3H)-dione；3′-O-benzyl-2′-O,4′-C-methyleneuridine；1-[(1S,3R,4R,7S)-1-(hydroxymethyl)-7-phenylmethoxy-2,5-dioxabicyclo[2.2.1]heptan-3-yl]pyrimidine-2,4-dione
• CAS: 200435-91-2
• 化学式: C₁₇H₁₈N₂O₆
• 分子量: 346.34
• InChiKey: KWQCNAXZKYMWAL-DLTWYDFYSA-N

物化性质

• 熔点：
  217-219 °C(Solv: methanol (67-56-1))
• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  97.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3'-O-benzyl-2'-O,4'-C-methyleneuridine 在 palladium on activated charcoal 吡啶 、 4-二甲氨基吡啶 、 硫酸氢铵 、 N-溴代丁二酰亚胺(NBS) 、 sodium azide 、 氢气 作用下， 以 甲醇 、 乙二醇二甲醚 、 水 为溶剂， 反应 142.0h， 生成 1-[(1R,4R,6R,7S)-4-[[bis(4-methoxyphenyl)phenylmethoxy]methyl]-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptan-6-yl]-5-methylpyrimidine-2,4-dione
  参考文献：
  名称：

  2′-O,4′-C-methylene bridged nucleic acid (2′,4′-BNA)

  摘要：

  For development of ideal antisense and antigene molecules, various chemical modifications of oligonucleotides have been studied. However, despite their importance. there is only limited information available on the tripler-forming ability of the conformationally restricted or locked oligonucleotides. We report herein that 2'-O,4'-C-methylene bridged nucleic acid (2',4'-BNA) modification of tripler-forming oligonucleotide: (TFO) significantly enhances the binding affinity towards target dsDNA. On T, measurements. the triplex with the 2',4'-BNA oligonucleotides were found to be stabilized with DeltaT(m)/modification of +4.3 to + 5 degreesC at pH 6.6 compared to the triplexes with the unmodified oligonucleotide. By means of gel-retardation assay, the binding constant of the 2'.4'-BNA oligonucleotide at pH 7.0 was at least 300-fold higher than that of the natural oligonucleotide. In addition, the 2',4'-BNA oligonucleotide clearly showed the inhibition of the NF-K-B transcription factor (p50)-target dsDNA binding by forming a stable tripler at pH 7.0. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00325-4
• 作为产物：
  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

文献信息

• Novel bicyclonucleoside and oligonucleotide analogue
  申请人：Takeshi IMANISHI

  公开号：US20030105309A1

  公开（公告）日：2003-06-05

  An oligo- or polynucleotide analogue having one or more structures of the general formula 1 where B is a pyrimidine or purine nucleic acid base, or an analogue thereof, is disclosed. The use of this analogue provides an oligonucleotide analogue antisense molecule, which is minimally hydrolyzable with an enzyme in vivo, has a high sense strand binding ability, and is easily synthesized.

  揭示了一种具有通式1的寡核苷酸或多核苷酸类似物，其中B是嘧啶或嘌呤核酸碱基，或其类似物。该类似物的使用提供了一种寡核苷酸类似物反义分子，在体内具有最小的水解能力，具有高的sense链结合能力，并且易于合成。
• Bicyclonucleoside and oligonucleotide analogues
  申请人：Takeshi Imanishi

  公开号：US06268490B1

  公开（公告）日：2001-07-31

  An oligo- or polynucleotide analogue having one or more structures of the general formula where B is a pyrimidine or purine nucleic acid base, or an analogue thereof, is disclosed. The use of this analogue provides an oligonucleotide analogue antisense molecule, which is minimally hydrolyzable with an enzyme in vivo, has a high sense strand binding ability, and is easily synthesized.

  揭示了一种具有一种或多种一般公式的结构的寡核苷酸或多核苷酸类似物，其中B是嘧啶或嘌呤核酸碱基或其类似物。该类似物的使用提供了一种寡核苷酸类似物反义分子，其在体内具有最小的水解能力，具有高的sense链结合能力，并且易于合成。
• Bicyclonucleoside and oligonucleotide analogue
  申请人：Imanishi Takeshi

  公开号：US06770748B2

  公开（公告）日：2004-08-03

  An oligo- or polynucleotide analogue having one or more structures of the general formula where B is a pyrimidine or purine nucleic acid base, or an analogue thereof, is disclosed. The use of this analogue provides an oligonucleotide analogue antisense molecule, which is minimally hydrolyzable with an enzyme in vivo, has a high sense strand binding ability, and is easily synthesized.

  揭示了一种具有一种或多种通式结构的寡核苷酸或多核苷酸类似物，其中B是嘧啶或嘌呤核酸碱基，或其类似物。使用这种类似物提供了一种寡核苷酸类似物反义分子，该分子在体内具有最小的水解能力，具有高的sense链结合能力，并且易于合成。
• 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。
• 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。