(1S,3R,4R,7S)-7-(benzyloxy)-1-[(benzyloxy)methyl]-3-(thymin-1-yl)-2,5-dioxabicyclo[2.2.1]heptane | 206055-62-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1S,3R,4R,7S)-7-(benzyloxy)-1-[(benzyloxy)methyl]-3-(thymin-1-yl)-2,5-dioxabicyclo[2.2.1]heptane
• 英文别名: (1S,3R,4R,7S)-7-benzyloxy-1-benzyloxymethyl-3-(thymine-1-yl)-2,5-dioxabicyclo[2.2.1]heptane；(1S,3R,4R,7S)-7-Benzyloxy-1-benzyloxymethyl-3-(thymin-1-yl)-2,5-dioxabicyclo-[2.2.1]heptane；5-methyl-1-[(1S,3R,4R,7S)-7-phenylmethoxy-1-(phenylmethoxymethyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl]pyrimidine-2,4-dione
• CAS: 206055-62-1
• 化学式: C₂₅H₂₆N₂O₆
• 分子量: 450.491
• InChiKey: DKVXNJXEAXHEHA-BEZYRKKYSA-N

物化性质

• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  86.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1S,3R,4R,7S)-7-(benzyloxy)-1-[(benzyloxy)methyl]-3-(thymin-1-yl)-2,5-dioxabicyclo[2.2.1]heptane 在 palladium dihydroxide 吡啶 、 氢气 作用下， 以 乙醇 为溶剂， 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：

  LNA (locked nucleic acids): synthesis and high-affinity nucleic acid recognition

  摘要：

  一类新型的核酸类似物，被称为LNA（锁定核酸），被引入了。根据Watson-Crick碱基配对规则，LNA与互补的DNA和RNA形成双链，具有显著增加的热稳定性和通常提高的选择性。

  DOI：

  10.1039/a708608c
• 作为产物：
  描述：

  3,5-di-O-benzyl-1,2-O-isopropylidene-4-C-methanesulfonyloxymethyl-α-D-ribofuranose 在 N,O-双三甲硅基乙酰胺 、 三氟甲磺酸三甲基硅酯 、 水 、 三乙基硼氢化锂 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 15.0h， 生成 (1S,3R,4R,7S)-7-(benzyloxy)-1-[(benzyloxy)methyl]-3-(thymin-1-yl)-2,5-dioxabicyclo[2.2.1]heptane
  参考文献：
  名称：

  含有新型 4'-C- 或 3'-C-(氨基烷基)-支化胸苷的寡核苷酸

  摘要：

  报道了四种新型 3'-C-支链和 4'-C-支链核苷的合成及其转化为相应的 3'-O-亚磷酰胺结构单元以用于自动寡核苷酸合成。4'-C-支化关键中间体11通过收敛策略合成并转化为其2'-O-甲基和2'-脱氧-2'-氟衍生物，从而制备出含有4'-的新型寡核苷酸类似物C-(氨基甲基)-2'-O-甲基单体X和4'-C-(氨基甲基)-2'-脱氧-2'-氟单体Y(方案2和3)。一般来说，与未修饰的参考相比，这些类似物对互补单链 DNA 和 RNA 的结合亲和力增加（表 1）。2'-O-甲基-RNA寡核苷酸中单体X或单体Y的存在对2'-O-甲基-RNA寡核苷酸对DNA和RNA的结合亲和力具有负面影响。从 3'-C-烯丙基衍生物 28 开始，合成了 3'-C-(3-氨基丙基)-保护的核苷和 3'-O-亚磷酰胺衍生物，从而产生了含有 3'-C-(3-氨基丙基）胸苷单体Z或相应的3'-C-（3-氨基丙基）-2'-O

  DOI：

  10.1002/(sici)1522-2675(20000119)83:1<128::aid-hlca128>3.0.co;2-q

文献信息

• LNA (Locked Nucleic Acids): Synthesis of the adenine, cytosine, guanine, 5-methylcytosine, thymine and uracil bicyclonucleoside monomers, oligomerisation, and unprecedented nucleic acid recognition
  作者：Alexei A. Koshkin、Sanjay K. Singh、Poul Nielsen、Vivek K. Rajwanshi、Ravindra Kumar、Michael Meldgaard、Carl Erik Olsen、Jesper Wengel

  DOI：10.1016/s0040-4020(98)00094-5

  日期：1998.4

  LNA (Locked Nucleic Acids), consisting of 2′-O,4′-C-methylene bicyclonucleoside monomers, is efficiently synthesized and its nucleic acid recognition potential evaluated for six different nucleobases, namely adenine, cytosine, guanine, 5-methylcytosine, thymine and uracil. Unprecedented increases (+3 to +8 °C per modification) in the thermal stability of duplexes towards both DNA and RNA were obtained

  由2'- O，4'- C-亚甲基双环核苷单体组成的LNA（锁定核酸）被有效合成，并评估了其对六种不同核碱基（腺嘌呤，胞嘧啶，鸟嘌呤，5-甲基胞嘧啶，胸腺嘧啶）的核酸识别潜力和尿嘧啶。当评估部分或完全修饰的LNA的混合序列时，双链体对DNA和RNA的热稳定性出现了前所未有的提高（每个修饰+3至+8°C）。错配序列的研究表明，与相应的未修饰参考链相比，LNA遵循具有普遍提高的选择性的Watson-Crick碱基配对规则。
• Design, Synthesis, and Properties of 2‘,4‘-BNA^NC:  A Bridged Nucleic Acid Analogue
  作者：S. M. Abdur Rahman、Sayori Seki、Satoshi Obika、Haruhisa Yoshikawa、Kazuyuki Miyashita、Takeshi Imanishi

  DOI：10.1021/ja710342q

  日期：2008.4.1

  incorporated into oligonucleotides, and their properties were investigated and compared with those of 2',4'-BNA (LNA)-modified oligonucleotides. Compared to 2',4'-BNA (LNA)-modified oligonucleotides, 2',4'-BNA(NC) congeners were found to possess: (i) equal or higher binding affinity against an RNA complement with excellent single-mismatch discriminating power, (ii) much better RNA selective binding, (iii)

  设计并合成了新型桥接核酸类似物 2',4'-BNA(NC)（2'-O,4'-C-氨基亚甲基桥接核酸），包含一个六元桥接结构和 NO 键有效地展示了构建全氢-1,2-恶嗪环的一锅式分子内 NC 键形成关键反应（11 和 12）。合成了 2',4'-BNA(NC) (2',4'-BNA(NC)[NH]、[NMe] 和 [NBn]) 的三种单体并将其掺入寡核苷酸中，并研究了它们的性质并与 2',4'-BNA (LNA) 修饰的寡核苷酸相比。与 2',4'-BNA (LNA) 修饰的寡核苷酸相比，发现 2',4'-BNA(NC) 同源物具有：(i) 对 RNA 补体具有相同或更高的结合亲和力，具有出色的单错配识别能力力量，(ii) 更好的 RNA 选择性结合，(iii) 更强且更具序列选择性的三链体形成特征，以及 (iv) 极高的核酸酶抗性，甚至高于 S(p)-硫代磷酸酯类似物。具有这些优异特性的
• Novel convenient syntheses of LNA [2.2.1]bicyclo nucleosides
  作者：Alexei A. Koshkin、Vivek K. Rajwanshi、Jesper Wengel

  DOI：10.1016/s0040-4039(98)00706-0

  日期：1998.6

  oligonucleotide analogue containing [2.2.1]bicyclo nucleoside monomers. A novel and significantly improved method for convergent synthesis of LNA [2.2.1]bicyclo nucleosides using a 4-C-tosyloxymethyl-1, 2-di-O-acetyl furanose as a key synthon is described. In addition, an alternative, robust linear approach allowing selective formation of the desired [2.2.1]bicyclo LNA nucleosides via a tricyclic nucleoside

  LNA（锁定核酸）是一种新型的寡核苷酸类似物，含有[2.2.1]双环核苷单体。描述了一种新颖且显着改进的方法，该方法使用4-C-甲苯磺酰氧基甲基-1，2-二-O-乙酰基呋喃糖作为关键合成子，聚合合成LNA [2.2.1]双环核苷。此外，介绍了一种替代的，稳健的线性方法，该方法允许通过三环核苷中间体选择性形成所需的[2.2.1]双环LNA核苷。
• Oligonucleotide analogues
  申请人：Wengel Jesper

  公开号：US20050287566A1

  公开（公告）日：2005-12-29

  The present invention relates to novel bicyclic and tricyclic nucleoside and nucleotide analogues as well as to oligonucleotides comprising such elements. The nucleotide analogues, LNAs (Locked Nucleoside Analogues), are able to provide valuable improvements to oligonucleotides with respect to affinity and specificity towards complementary RNA and DNA oligomers. The novel type of LNA modified oligonucleotides, as well as the LNAs as such, are useful in a wide range of diagnostic applications as well as therapeutic applications. Among these can be mentioned antisense applications, PCR applications, strand displacement oligomers, as substrates for nucleic acid polymerases, as nucleotide based drugs, etc. The present invention also relates to such applications.

  本发明涉及新型的双环和三环核苷酸和核苷酸类似物，以及包含这些元素的寡核苷酸。这些核苷酸类似物，即锁定核苷酸类似物（LNAs），能够为寡核苷酸提供与互补RNA和DNA寡聚物的亲和力和特异性方面的有价值的改进。这种新型的LNA修饰的寡核苷酸以及LNA本身在广泛的诊断应用和治疗应用中非常有用。其中包括反义应用、PCR应用、链置换寡聚物、作为核酸聚合酶的底物、作为基于核苷酸的药物等。本发明还涉及这些应用。
• OLIGONUCLEOTIDE ANALOGUES
  申请人：Wengel Jesper

  公开号：US20100279895A1

  公开（公告）日：2010-11-04

  The present invention relates to novel bicyclic and tricyclic nucleoside and nucleotide analogues as well as to oligonucleotides comprising such elements. The nucleotide analogues, LNAs (Locked Nucleoside Analogues), are able to provide valuable improvements to oligonucleotides with respect to affinity and specificity towards complementary RNA and DNA oligomers. The novel type of LNA modified oligonucleotides, as well as the LNAs as such, are useful in a wide range of diagnostic applications as well as therapeutic applications. Among these can be mentioned antisense applications, PCR applications, strand displacement oligomers, as substrates for nucleic acid polymerases, as nucleotide based drugs, etc. The present invention also relates to such applications.

  本发明涉及新型的双环和三环核苷酸和核苷酸类似物，以及包含这些元素的寡核苷酸。这些核苷酸类似物，即LNAs（锁定核苷酸类似物），能够为寡核苷酸提供与互补RNA和DNA寡聚物相比亲和力和特异性的有价值的改进。这种新型的LNA修饰的寡核苷酸以及LNAs本身在广泛的诊断应用和治疗应用中都有用途。其中可以提到反义应用、PCR应用、链位移寡聚物、作为核酸聚合酶底物、作为核苷酸基药物等。本发明还涉及这些应用。