(1R,3R,4R,7S)-7-(tert-butyldimethylsilyloxy)-1-[1-(S)-hydroxyethyl]-3-(uracil-1-yl)-2,5-dioxabicyclo[2.2.1]heptane | 956484-87-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1R,3R,4R,7S)-7-(tert-butyldimethylsilyloxy)-1-[1-(S)-hydroxyethyl]-3-(uracil-1-yl)-2,5-dioxabicyclo[2.2.1]heptane
• 英文别名: 1-[(1R,3R,4R,7S)-7-[tert-butyl(dimethyl)silyl]oxy-1-[(1S)-1-hydroxyethyl]-2,5-dioxabicyclo[2.2.1]heptan-3-yl]pyrimidine-2,4-dione
• CAS: 956484-87-0
• 化学式: C₁₇H₂₈N₂O₆Si
• 分子量: 384.505
• InChiKey: HHRHURXZVSWAPF-UPMLDKDTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.97
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  97.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1R,3R,4R,7S)-7-(tert-butyldimethylsilyloxy)-1-[1-(S)-hydroxyethyl]-3-(uracil-1-yl)-2,5-dioxabicyclo[2.2.1]heptane 在 triethylamine tris(hydrogen fluoride) 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以93%的产率得到
  参考文献：
  名称：

  Configuration of the 5′-Methyl Group Modulates the Biophysical and Biological Properties of Locked Nucleic Acid (LNA) Oligonucleotides

  摘要：

  As part of a program aimed at exploring the structure activity relationships of 2',4'-bridged nucleic acid (BNA) containing antisense oligonucleotides (ASOs), we report the synthesis and biophysical and biological properties of R- and S-5'-Me LNA modified oligonucleotides. We show that introduction of a methyl group in the (S) configuration at the 5'-position is compatible with the high affinity recognition of complementary nucleic acids observed with LNA. In contrast, introduction of a methyl group in the (R) configuration reversed the stabilization effect of LNA. NMR studies indicated that the R-5'-Me group changes the orientation around torsion angle gamma from the +sc to the ap range at the nucleoside level, and this may in part be responsible for the poor hybridization behavior exhibited by this modification. In animal experiments, S-5'-Me-LNA, modified gapmer antisense olignucleotides showed slightly reduced potency relative to the sequence matched LNA ASOs while improving the therapeutic profile.

  DOI：

  10.1021/jm101207e
• 作为产物：
  描述：

  (1R,3R,4R,7S)-1-[1-(S)-(benzoyloxy)ethyl]-7-(tert-butyldimethylsilyloxy)-3-(uracil-1-yl)-2,5-dioxabicyclo[2.2.1]heptane 在 氨 作用下， 以 甲醇 为溶剂， 反应 120.0h， 以90%的产率得到(1R,3R,4R,7S)-7-(tert-butyldimethylsilyloxy)-1-[1-(S)-hydroxyethyl]-3-(uracil-1-yl)-2,5-dioxabicyclo[2.2.1]heptane
  参考文献：
  名称：

  Configuration of the 5′-Methyl Group Modulates the Biophysical and Biological Properties of Locked Nucleic Acid (LNA) Oligonucleotides

  摘要：

  As part of a program aimed at exploring the structure activity relationships of 2',4'-bridged nucleic acid (BNA) containing antisense oligonucleotides (ASOs), we report the synthesis and biophysical and biological properties of R- and S-5'-Me LNA modified oligonucleotides. We show that introduction of a methyl group in the (S) configuration at the 5'-position is compatible with the high affinity recognition of complementary nucleic acids observed with LNA. In contrast, introduction of a methyl group in the (R) configuration reversed the stabilization effect of LNA. NMR studies indicated that the R-5'-Me group changes the orientation around torsion angle gamma from the +sc to the ap range at the nucleoside level, and this may in part be responsible for the poor hybridization behavior exhibited by this modification. In animal experiments, S-5'-Me-LNA, modified gapmer antisense olignucleotides showed slightly reduced potency relative to the sequence matched LNA ASOs while improving the therapeutic profile.

  DOI：

  10.1021/jm101207e

文献信息

• Configuration of the 5′-Methyl Group Modulates the Biophysical and Biological Properties of Locked Nucleic Acid (LNA) Oligonucleotides
  作者：Punit P. Seth、Charles R. Allerson、Andrew Siwkowski、Guillermo Vasquez、Andres Berdeja、Michael T. Migawa、Hans Gaus、Thazha P. Prakash、Balkrishen Bhat、Eric E. Swayze

  DOI：10.1021/jm101207e

  日期：2010.12.9

  As part of a program aimed at exploring the structure activity relationships of 2',4'-bridged nucleic acid (BNA) containing antisense oligonucleotides (ASOs), we report the synthesis and biophysical and biological properties of R- and S-5'-Me LNA modified oligonucleotides. We show that introduction of a methyl group in the (S) configuration at the 5'-position is compatible with the high affinity recognition of complementary nucleic acids observed with LNA. In contrast, introduction of a methyl group in the (R) configuration reversed the stabilization effect of LNA. NMR studies indicated that the R-5'-Me group changes the orientation around torsion angle gamma from the +sc to the ap range at the nucleoside level, and this may in part be responsible for the poor hybridization behavior exhibited by this modification. In animal experiments, S-5'-Me-LNA, modified gapmer antisense olignucleotides showed slightly reduced potency relative to the sequence matched LNA ASOs while improving the therapeutic profile.