(1S,3R,4S,7R)-3-[5-(3-cholesterylcarbonylaminopropyn-1-yl)uracil-1-yl]-1-(4,4′-dimethoxytrityloxymethyl)-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptane | 1275611-20-5

• 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: (1S,3R,4S,7R)-3-[5-(3-cholesterylcarbonylaminopropyn-1-yl)uracil-1-yl]-1-(4,4′-dimethoxytrityloxymethyl)-7-hydroxy-2,5-dioxabicyclo[2.2.1]heptane
• CAS: 1275611-20-5
• 化学式: C₆₂H₇₇N₃O₁₀
• 分子量: 1024.31
• InChiKey: PCIPYKNERMHLFG-WBDWSRIGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.08
• 重原子数：
  75.0
• 可旋转键数：
  16.0
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  159.57
• 氢给体数：
  3.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  (1S,3R,4S,7R)-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 3.0h， 以57%的产率得到(1S,3R,4S,7R)-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：

  C5-Alkynyl-Functionalized α-L-LNA: Synthesis, Thermal Denaturation Experiments and Enzymatic Stability

  摘要：

  Major efforts are currently being devoted to improving the binding affinity, target specificity, and enzymatic stability of oligonucleotides used for nucleic acid targeting applications in molecular biology, biotechnology, and medicinal chemistry. One of the most popular strategies toward this end has been to introduce additional modifications to the sugar ring of affinity-inducing conformationally restricted nucleotide building blocks such as locked nucleic acid (LNA). In the preceding article in this issue, we introduced a different strategy toward this end, i.e., C5-functionalization of LNA uridines. In the present article, we extend this strategy to alpha-L-LNA: i.e., one of the most interesting diastereomers of LNA. alpha-L-LNA uridine monomers that are conjugated to small C5-alkynyl substituents induce significant improvements in target affinity, binding specificity, and enzymatic stability relative to conventional alpha-L-LNA. The results from the back-to-back articles therefore suggest that C5-functionalization of pyrimidines is a general and synthetically straightforward approach to modulate biophysical properties of oligonucleotides modified with LNA or other conformationally restricted monomers.

  DOI：

  10.1021/jo5006153
• 作为产物：
  描述：

  (1S,3R,4S,7R)-7-benzyloxy-1-methanesulfonyloxymethyl-3-(uracil-1-yl)-2,5-dioxabicyclo[2.2.1]heptane 在 吡啶 、 copper(l) iodide 、 四(三苯基膦)钯 、 ammonium cerium (IV) nitrate 、 palladium on carbon 、 氨 、 碘 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 甲酸 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 112.83h， 生成 (1S,3R,4S,7R)-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：

  C5-Alkynyl-Functionalized α-L-LNA: Synthesis, Thermal Denaturation Experiments and Enzymatic Stability

  摘要：

  Major efforts are currently being devoted to improving the binding affinity, target specificity, and enzymatic stability of oligonucleotides used for nucleic acid targeting applications in molecular biology, biotechnology, and medicinal chemistry. One of the most popular strategies toward this end has been to introduce additional modifications to the sugar ring of affinity-inducing conformationally restricted nucleotide building blocks such as locked nucleic acid (LNA). In the preceding article in this issue, we introduced a different strategy toward this end, i.e., C5-functionalization of LNA uridines. In the present article, we extend this strategy to alpha-L-LNA: i.e., one of the most interesting diastereomers of LNA. alpha-L-LNA uridine monomers that are conjugated to small C5-alkynyl substituents induce significant improvements in target affinity, binding specificity, and enzymatic stability relative to conventional alpha-L-LNA. The results from the back-to-back articles therefore suggest that C5-functionalization of pyrimidines is a general and synthetically straightforward approach to modulate biophysical properties of oligonucleotides modified with LNA or other conformationally restricted monomers.

  DOI：

  10.1021/jo5006153