(1R,3R,4R,7S)-3-[5-(3-cholesterylcarbonylaminopropyn-1-yl)uracil-1-yl]-1-(4,4′-dimethoxytrityloxymethyl)-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptane | 1252654-41-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (1R,3R,4R,7S)-3-[5-(3-cholesterylcarbonylaminopropyn-1-yl)uracil-1-yl]-1-(4,4′-dimethoxytrityloxymethyl)-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptane
• 英文别名: [(3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl] N-[3-[1-[(1R,3R,4R,7S)-1-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptan-3-yl]-2,4-dioxopyrimidin-5-yl]prop-2-ynyl]carbamate
• CAS: 1252654-41-3
• 化学式: C₆₂H₇₇N₃O₁₀
• 分子量: 1024.31
• InChiKey: PCIPYKNERMHLFG-KLFCYUDCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.3
• 重原子数：
  75
• 可旋转键数：
  18
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  154
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (1R,3R,4R,7S)-3-[5-(3-cholesterylcarbonylaminopropyn-1-yl)uracil-1-yl]-1-(4,4′-dimethoxytrityloxymethyl)-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptane 、 2-氰乙基N,N-二异丙基氯亚磷酰胺 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以66%的产率得到(1R,3R,4R,7S)-3-[5-(3-cholesterylcarbonylaminopropyn-1-yl)-uracil-1-yl]-7-[2-cyanoethoxy(diisopropylamino)phosphinoxy]-1-(4,4'-dimethoxytrityloxymethyl)-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 、 碘 、 三乙胺 作用下， 以 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.67h， 生成 (1R,3R,4R,7S)-3-[5-(3-cholesterylcarbonylaminopropyn-1-yl)uracil-1-yl]-1-(4,4′-dimethoxytrityloxymethyl)-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

• 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.