5'-O-(4,4'-dimethoxytrityl)-2'-O,4'-C-ethylene-5-methyluridine-3'-O-(2-cyanoethyl N,N-diisopropyl)phosphoramidite

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 5'-O-(4,4'-dimethoxytrityl)-2'-O,4'-C-ethylene-5-methyluridine-3'-O-(2-cyanoethyl N,N-diisopropyl)phosphoramidite
• 英文别名: 3-[[(1R,5R,7R,8S)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-7-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,6-dioxabicyclo[3.2.1]octan-8-yl]oxy-[di(propan-2-yl)amino]phosphanyl]oxypropanenitrile
• 化学式: C₄₂H₅₁N₄O₉P
• 分子量: 786.862
• InChiKey: BCXPUDBJUMTTSQ-RWDMRMDHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  56
• 可旋转键数：
  17
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  141
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  (3aR,5R,6S,6aR)-6-(benzyloxy)-5-((benzyloxy)methyl)-2,2-dimethyl-5-vinyltetrahydrofuro[2,3-d][1,3]dioxole 在 palladium dihydroxide 吡啶 、 sodium hydroxide 、 9-borabicyclo[3.3.1]nonane dimer 、 三氟甲磺酸三甲基硅酯 、 硫酸 、 二异丙基铵盐四氮唑 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 溶剂黄146 、 1,2-二氯乙烷 为溶剂， 生成 5'-O-(4,4'-dimethoxytrityl)-2'-O,4'-C-ethylene-5-methyluridine-3'-O-(2-cyanoethyl N,N-diisopropyl)phosphoramidite
  参考文献：
  名称：

  2′-O,4′-C-ethylene-bridged nucleic acids (ENA): highly nuclease-resistant and thermodynamically stable oligonucleotides for antisense drug

  摘要：

  To develop antisense oligonucleotides, novel nucleosides, 2'-O-4'-C-ethylene nucleosides and their corresponding phosphoramidites, were synthesized as building blocks. The H-1 NMR analysis showed that the 2'-O,4'-C-ethylene linkage of these nucleosides restricts the sugar puckering to the N-conformation as well as the linkage of 2'-O,4'-C-methylene nucleosides which are known as bridged nucleic acids (BNA) or locked nucleic acids (LNA). The ethylene-bridged nucleic acids (ENA) showed a high binding affinity for the complementary RNA strand (DeltaT(m) = +5.2 degreesC/modification) and were more nuclease-resistant than natural DNA and BNA/LNA. These results indicate that ENA have better properties as antisense oligonucleotides than BNA/LNA. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00683-7

文献信息

• Synthesis and properties of 2′-O,4′-C-Ethylene-Bridged nucleic acids (ENA) as effective antisense oligonucleotides
  作者：Koji Morita、Miho Takagi、Chikako Hasegawa、Masakatsu Kaneko、Shinya Tsutsumi、Junko Sone、Tomio Ishikawa、Takeshi Imanishi、Makoto Koizumi

  DOI：10.1016/s0968-0896(03)00115-9

  日期：2003.5

  bridged nucleic acids (2',4'-BNA) or locked nucleic acids (LNA). Both the 2'-O,4'-C-ethylene- and propylene-linkage within these nucleosides restrict the sugar puckering to the N-conformation of RNA as do 2',4'-BNA/LNA. Furthermore, ethylene-bridged nucleic acids (ENA) having 2'-O,4'-C-ethylene nucleosides had considerably increased the affinity to complementary RNA, and were as high as that of 2',4'-BNA/LNA

  合成了新型双环核苷，2'-O，4'-C-乙烯核苷和2'-O，4'-C-丙烯核苷，作为反义寡核苷酸的构建基块，以进一步优化2'-O，4'-桥连核酸（2'，4'-BNA）或锁定核酸（LNA）的C-亚甲基键。这些核苷中的2'-O，4'-C-乙烯-和丙烯键都将糖的褶皱限制为RNA的N-构象，就像2'，4'-BNA / LNA一样。此外，具有2'-O，4'-C-乙烯核苷的乙烯桥连核酸（ENA）大大提高了对互补RNA的亲和力，并且与2'，4'-BNA / LNA（DeltaT （m）＝ + 3，每次修改约5摄氏度。另一方面，添加2'-O，4' 寡核苷酸中的-C-丙烯修饰导致与互补RNA的亲和力降低。至于对核酸酶的稳定性，在寡核苷酸中掺入一个2'-O，4'-C-乙烯或一个2'-O，4'-C-丙烯核苷可显着提高其对核酸外切酶的抗性至大于2'的程度。 ，4'-BNA / LNA。这些结果表明ENA比2'，4'-BNA
• MODIFIED DOUBLE-STRANDED POLYNUCLEOTIDE
  申请人：Koizumi Makoto

  公开号：US20120220649A1

  公开（公告）日：2012-08-30

  The present invention provides a double-stranded polynucleotide having a sense strand polynucleotide consisting of a nucleotide sequence complementary to a target sequence in a target gene, and an antisense strand polynucleotide having a nucleotide sequence complementary to the sense strand polynucleotide, wherein an aryl or heteroaryl compound is bound to a phosphate group at the 5′-end of the antisense strand polynucleotide.

  本发明提供了一种双链聚核苷酸，其具有一个具有与目标基因中的目标序列互补的核苷酸序列的正链聚核苷酸，以及一个具有与正链聚核苷酸互补的核苷酸序列的反义链聚核苷酸，其中一种芳基或杂环芳基化合物结合到反义链聚核苷酸的5'-末端的磷酸基团上。
• Synthesis of 2′,4′-Propylene-Bridged (Carba-ENA) Thymidine and Its Analogues: The Engineering of Electrostatic and Steric Effects at the Bottom of the Minor Groove for Nuclease and Thermodynamic Stabilities and Elicitation of RNase H
  作者：Yi Liu、Jianfeng Xu、Mansoureh Karimiahmadabadi、Chuanzheng Zhou、Jyoti Chattopadhyaya

  DOI：10.1021/jo101207d

  日期：2010.11.5

  any, effect on nuclease resistance but 8′S-OH resulted in significantly decreased nucleolytic stability; and (3) 8′-NH2 substituted carba-ENA leads to obvious loss in the nuclease resistance. The RNA strand in all of the carba-ENA derivatives modified AON:RNA hybrid duplexes can be digested by RNase H1 with high efficiency, even at twice the rate of those of the native and ENA modified counterpart.

  2'，4'-丙烯桥胸苷（carba-ENA-T）和5个8'-Me / NH 2通过将分子内自由基加成到束缚的肟-醚的C═N中，已经制备了/ OH修饰的氨基-ENA-T类似物。这些碳烯-ENA核苷随后被掺入15mer寡脱氧核苷酸（AON）中，并且与天然和ENA对应物相比，已研究了它们对cDNA和RNA的亲和力，核酸酶抗性和RNase H募集能力。这些碳烯-ENA修饰的AON具有高度的RNA选择性，因为它们都对AON：RNA双链体产生轻微的热稳定作用，但对AON：DNA双链体产生相当大的去稳定作用。发现在carba-ENA-T上不同的C8'取代基（在小凹槽的底部）仅导致AON：RNA双链体的热稳定性变化很小。但是，我们 观察到，亲代碳酸酯-ENA-T修饰的AONs表现出比ENA-T修饰的对应物更高的核酸分解稳定性。不仅取决于化学性质，而且取决于C8'取代基的立体化学取向，C8'取代基还可以进一
• Efficient Divergent Synthesis of 2′-<i>O</i>,4′-<i>C</i>-Ethylene-Bridged Nucleic Acid (ENA) Phosphoramidites
  作者：Yuzo Abe、Kazutoshi Ukai、Makoto Michida

  DOI：10.1021/acs.oprd.2c00013

  日期：2022.4.15

  developed a highly efficient synthetic method for ENA phosphoramidites. The basic concept of the new synthetic route is “divergent synthesis” for the preparation of four types of monomers such as A, G, C, and T. We applied stereoselective glycosylation reactions without utilizing neighboring group participation to set a common intermediate in the downstream of the route.

  2'- O ,4'- C-乙烯桥连核酸（ENA）亚磷酰胺是第一三共发现的极具前景的修饰核酸单体。为了提高生产效率，我们开发了一种高效的 ENA 亚磷酰胺合成方法。新合成路线的基本概念是“发散合成”，用于制备 A、G、C 和 T 四种单体。我们应用立体选择性糖基化反应，不利用相邻基团参与，在下游设置共同的中间体的路线。
• Probes, libraries and kits for analysis of mixtures of nucleic acids and methods for constructing the same
  申请人：Ramsing Birger Niels

  公开号：US20060166238A1

  公开（公告）日：2006-07-27

  The invention relates to nucleic acid probes, nucleic acid probe libraries, and kits for detecting, classifying, or quantifying components in a complex mixture of nucleic acids, such as a transcriptome, and methods of using the same. The invention also relates to methods of identifying nucleic acid probes useful in the probe libraries and to methods of identifying a means for detection of a given nucleic acid.

  本发明涉及核酸探针、核酸探针库和用于检测、分类或定量核酸复杂混合物（例如转录组）中的组分的工具箱以及使用它们的方法。本发明还涉及识别有用于探针库的核酸探针的方法，以及识别给定核酸检测手段的方法。