5′-O-(4,4′-dimethoxytrityl)-2′-O,4′-C-methylenethymidine-3′-[O-(2-cyanoethyl)-(N,N-diisopropyl)]-phosphoramidite | 206055-76-7

• 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-methylenethymidine-3′-[O-(2-cyanoethyl)-(N,N-diisopropyl)]-phosphoramidite
• 英文别名: 3'-O-[2-cyanoethoxy(diisopropylamino)phosphino]-5'-O-(4,4'-dimethoxytrityl)-2'-O,4'-C-methyleneuridine；5'-O-DMTr-2'-O,4'-C-methyleneuridine 3'-CE-phosphoramidite；3-[[(1R,3R,4R,7S)-1-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3-(2,4-dioxopyrimidin-1-yl)-2,5-dioxabicyclo[2.2.1]heptan-7-yl]oxy-[di(propan-2-yl)amino]phosphanyl]oxypropanenitrile
• CAS: 206055-76-7
• 化学式: C₄₀H₄₇N₄O₉P
• 分子量: 758.808
• InChiKey: ROCIJWWVBQZMMI-PUIMFIDCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  54
• 可旋转键数：
  17
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  141
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  4-(2,3-dihydrophytyloxy)benzoyl chloride 、 5′-O-(4,4′-dimethoxytrityl)-2′-O,4′-C-methylenethymidine-3′-[O-(2-cyanoethyl)-(N,N-diisopropyl)]-phosphoramidite 在 吡啶 、 N,N-二异丙基乙胺 作用下， 反应 9.0h， 以65.5%的产率得到5'-O-(4,4'-dimethoxytrityl)-N³-[4-(2,3-dihydrophytyloxy)benzoyl]-2'-O,4'-C-methylenethymidine-3'-O-[(2-cyanoethyl)-N,N-diisopropylphosphoramidite]
  参考文献：
  名称：

  Oligonucleotide with protected base

  摘要：

  本发明提供了一种用于延伸的受保护核苷酸，可以通过液液萃取操作高效地和高产率地纯化，并且可以通过磷酰胺酯法实现寡核苷酸的生产方法。已经发现，上述问题可以通过包含受保护碱基和/或在3'-位置含有支链含芳基团的特定寡核苷酸来解决。

  公开号：

  US09371353B2
• 作为产物：
  描述：

  Benzoic acid (1R,3R,4R,7S)-3-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-7-hydroxy-2,5-dioxa-bicyclo[2.2.1]hept-1-ylmethyl ester 在 吡啶 、 甲醇 、 sodium methylate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 生成 5′-O-(4,4′-dimethoxytrityl)-2′-O,4′-C-methylenethymidine-3′-[O-(2-cyanoethyl)-(N,N-diisopropyl)]-phosphoramidite
  参考文献：
  名称：

  DNA triplex structures are stabilized by the incorporation of 3′-endo blocked pyrimidine nucleosides in the hoogsteen strand

  摘要：

  A short route to pyrimidine locked nucleosides has been developed for their incorporation in tripler forming oligonucleotides (TFO). Compared to oligonucleotides built with standard nucleosides, the modified TFOs containing 3'-endo blocked residues formed, with their corresponding DNA duplexes, more stable triple helix systems, an effect which might be ascribed to the 3'-endo pucker of the modified nucleoside residues. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00434-0

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。
• NOVEL BICYCLONUCLEOSIDE AND OLIGONUCLEOTIDE ANALOGUES
  申请人：Imanishi, Takeshi

  公开号：EP1013661A1

  公开（公告）日：2000-06-28

  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 oligonuoleotide analogue antisense molecule, which is minimally hydrolyzable with an enzyme in vivo, has a high sense strand binding ability, and is easily synthesized.

  具有一个或多个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、 或其类似物。使用这种类似物可以得到一种寡核苷酸类似物反义分子，它在体内与酶的水解程度极低，具有较高的有义链结合能力，并且易于合成。
• Novel Bicyclonucleoside and Oligonucleotide Analogue
  申请人：Exiqon A/S

  公开号：EP2295441A2

  公开（公告）日：2011-03-16

  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.

  具有一个或多个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、 或其类似物。使用这种类似物可以得到一种寡核苷酸类似物反义分子，它在体内与酶的水解程度极低，具有较高的有义链结合能力，并且易于合成。
• Novel bicyclonucleoside and oligonnucleotide analogue
  申请人：Exiqon A/S

  公开号：EP2361921A2

  公开（公告）日：2011-08-31

  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.

  具有一个或多个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、 或其类似物。使用这种类似物可以得到一种寡核苷酸类似物反义分子，它在体内与酶的水解程度极低，具有较高的有义链结合能力，并且易于合成。
• 2′-O,4′-C-methylene bridged nucleic acid (2′,4′-BNA)
  作者：Satoshi Obika、Takeshi Uneda、Tomomi Sugimoto、Daishu Nanbu、Takashi Minami、Takefumi Doi、Takeshi Imanishi

  DOI：10.1016/s0968-0896(00)00325-4

  日期：2001.4

  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.