(1R,3R,4R,7S)-1-(4,4'-dimethoxytrityloxymethyl)-3-(5-ethynyluracil-1-yl)-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptane | 1202937-25-4

• 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: (1R,3R,4R,7S)-1-(4,4'-dimethoxytrityloxymethyl)-3-(5-ethynyluracil-1-yl)-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptane
• 英文别名: 1-[(1R,3R,4R,7S)-1-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptan-3-yl]-5-ethynylpyrimidine-2,4-dione
• CAS: 1202937-25-4
• 化学式: C₃₃H₃₀N₂O₈
• 分子量: 582.61
• InChiKey: LJCHDLILPPXLSL-NDYSUJMESA-N

物化性质

• 密度：
  1.41±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  43
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (1R,3R,4R,7S)-1-(4,4'-dimethoxytrityloxymethyl)-3-(5-ethynyluracil-1-yl)-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptane 在 copper(II) sulfate 、 sodium ascorbate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 叔丁醇 为溶剂， 反应 4.5h， 生成 (1R,3R,4R,7S)-7-[2-cyanoethoxy(diisopropylamino)phosphinoxy]-1-(4,4'-dimethoxytrityloxymethyl)-3-[5-(1-(1-pyrenyl)-1H-1,2,3-triazol-4-yl)uracil-1-yl]-2,5-dioxabicyclo[2.2.1]heptane
  参考文献：
  名称：

  Synthesis and Biophysical Properties of C5-Functionalized LNA (Locked Nucleic Acid)

  摘要：

  Oligonucleotides modified with conformationally restricted nucleotides such as locked nucleic acid (LNA) monomers are used extensively in molecular biology and medicinal chemistry to modulate gene expression at the RNA level. Major efforts have been devoted to the design of LNA derivatives that induce even higher binding affinity and specificity, greater enzymatic stability, and more desirable pharmacokinetic profiles. Most of this work has focused on modifications of LNA's oxymethylene bridge. Here, we describe an alternative approach for modulation of the properties of LNA: i.e., through functionalization of LNA nucleobases. Twelve structurally diverse CS-functionalized LNA uridine (U) phosphoramidites were synthesized and incorporated into oligodeoxyribonucleotides (ONs), which were then characterized with respect to thermal denaturation, enzymatic stability, and fluorescence properties. ONs modified with monomers that are conjugated to small alkynes display significantly improved target affinity, binding specificity, and protection against 3'-exonucleases relative to regular LNA. In contrast, ONs modified with monomers that are conjugated to bulky hydrophobic alkynes display lower target affinity yet much greater 3'-exonuclease resistance. ONs modified with C5-fluorophore-functionalized LNA-U monomers enable fluorescent discrimination of targets with single nucleotide polymorphisms (SNPs). In concert, these properties render C5-functionalized LNA as a promising class of building blocks for RNA-targeting applications and nucleic acid diagnostics.

  DOI：

  10.1021/jo500614a
• 作为产物：
  描述：

  1-(2’-O,4-C-甲桥-BETA-D-呋喃核糖基)尿苷 在 吡啶 、 copper(l) iodide 、 四(三苯基膦)钯 、 ammonium cerium (IV) nitrate 、 四丁基氟化铵 、 碘 、 三乙胺 作用下， 以 四氢呋喃 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.67h， 生成 (1R,3R,4R,7S)-1-(4,4'-dimethoxytrityloxymethyl)-3-(5-ethynyluracil-1-yl)-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptane
  参考文献：
  名称：

  Synthesis and Biophysical Properties of C5-Functionalized LNA (Locked Nucleic Acid)

  摘要：

  Oligonucleotides modified with conformationally restricted nucleotides such as locked nucleic acid (LNA) monomers are used extensively in molecular biology and medicinal chemistry to modulate gene expression at the RNA level. Major efforts have been devoted to the design of LNA derivatives that induce even higher binding affinity and specificity, greater enzymatic stability, and more desirable pharmacokinetic profiles. Most of this work has focused on modifications of LNA's oxymethylene bridge. Here, we describe an alternative approach for modulation of the properties of LNA: i.e., through functionalization of LNA nucleobases. Twelve structurally diverse CS-functionalized LNA uridine (U) phosphoramidites were synthesized and incorporated into oligodeoxyribonucleotides (ONs), which were then characterized with respect to thermal denaturation, enzymatic stability, and fluorescence properties. ONs modified with monomers that are conjugated to small alkynes display significantly improved target affinity, binding specificity, and protection against 3'-exonucleases relative to regular LNA. In contrast, ONs modified with monomers that are conjugated to bulky hydrophobic alkynes display lower target affinity yet much greater 3'-exonuclease resistance. ONs modified with C5-fluorophore-functionalized LNA-U monomers enable fluorescent discrimination of targets with single nucleotide polymorphisms (SNPs). In concert, these properties render C5-functionalized LNA as a promising class of building blocks for RNA-targeting applications and nucleic acid diagnostics.

  DOI：

  10.1021/jo500614a

文献信息

• Optimized DNA-targeting using triplex forming C5-alkynyl functionalized LNA
  作者：Sujay P. Sau、Pawan Kumar、Brooke A. Anderson、Michael E. Østergaard、Lee Deobald、Andrzej Paszczynski、Pawan K. Sharma、Patrick J. Hrdlicka

  DOI：10.1039/b917312a

  日期：——

  Triplex forming oligonucleotides (TFOs) modified with C5-alkynyl functionalized LNA (locked nucleic acid) monomers display extraordinary thermal affinity toward double stranded DNA targets, excellent discrimination of Hoogsteen-mismatched targets, and high stability against 3′-exonucleases.

  用 C5-炔基官能化 LNA（锁定核酸）单体修饰的三重形成寡核苷酸（TFO）对双链 DNA 靶标具有超强的热亲和力，对胡格氏错配靶标具有出色的识别能力，对 3′-外切酶具有高度稳定性。
• [EN] NUCLEOBASE-FUNCTIONALIZED CONFORMATIONALLY RESTRICTED NUCLEOTIDES AND OLIGONUCLEOTIDES FOR TARGETING NUCLEIC ACIDS<br/>[FR] NUCLÉOTIDES ET OLIGONUCLÉOTIDES À CONFORMATION RESTREINTE À FONCTIONNALITÉ NUCLÉOBASE POUR CIBLER DES ACIDES NUCLÉIQUES
  申请人：UNIV IDAHO

  公开号：WO2011032034A3

  公开（公告）日：2011-07-21
• Synthesis and Biophysical Properties of C5-Functionalized LNA (Locked Nucleic Acid)
  作者：Pawan Kumar、Michael E. Østergaard、Bharat Baral、Brooke A. Anderson、Dale C. Guenther、Mamta Kaura、Daniel J. Raible、Pawan K. Sharma、Patrick J. Hrdlicka

  DOI：10.1021/jo500614a

  日期：2014.6.6

  Oligonucleotides modified with conformationally restricted nucleotides such as locked nucleic acid (LNA) monomers are used extensively in molecular biology and medicinal chemistry to modulate gene expression at the RNA level. Major efforts have been devoted to the design of LNA derivatives that induce even higher binding affinity and specificity, greater enzymatic stability, and more desirable pharmacokinetic profiles. Most of this work has focused on modifications of LNA's oxymethylene bridge. Here, we describe an alternative approach for modulation of the properties of LNA: i.e., through functionalization of LNA nucleobases. Twelve structurally diverse CS-functionalized LNA uridine (U) phosphoramidites were synthesized and incorporated into oligodeoxyribonucleotides (ONs), which were then characterized with respect to thermal denaturation, enzymatic stability, and fluorescence properties. ONs modified with monomers that are conjugated to small alkynes display significantly improved target affinity, binding specificity, and protection against 3'-exonucleases relative to regular LNA. In contrast, ONs modified with monomers that are conjugated to bulky hydrophobic alkynes display lower target affinity yet much greater 3'-exonuclease resistance. ONs modified with C5-fluorophore-functionalized LNA-U monomers enable fluorescent discrimination of targets with single nucleotide polymorphisms (SNPs). In concert, these properties render C5-functionalized LNA as a promising class of building blocks for RNA-targeting applications and nucleic acid diagnostics.