[(2R,3R,4R,5R,6R)-5-acetamido-3,4-diacetyloxy-6-[2-[2-[4-[[[(2R,3R,4R,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-(2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxycarbonylamino]methyl]triazol-1-yl]ethoxy]ethoxy]oxan-2-yl]methyl acetate | 1268342-15-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [(2R,3R,4R,5R,6R)-5-acetamido-3,4-diacetyloxy-6-[2-[2-[4-[[[(2R,3R,4R,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-(2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxycarbonylamino]methyl]triazol-1-yl]ethoxy]ethoxy]oxan-2-yl]methyl acetate
• CAS: 1268342-15-9
• 化学式: C₃₇H₅₇N₇O₁₇Si
• 分子量: 899.982
• InChiKey: SHPXSDVKIBLOFA-FUSBJJJXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.61
• 重原子数：
  62
• 可旋转键数：
  24
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  293
• 氢给体数：
  4
• 氢受体数：
  19

反应信息

• 作为反应物：
  描述：

  [(2R,3R,4R,5R,6R)-5-acetamido-3,4-diacetyloxy-6-[2-[2-[4-[[[(2R,3R,4R,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-(2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxycarbonylamino]methyl]triazol-1-yl]ethoxy]ethoxy]oxan-2-yl]methyl acetate 、 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 4.0h， 以83%的产率得到
  参考文献：
  名称：

  Versatile Site-Specific Conjugation of Small Molecules to siRNA Using Click Chemistry

  摘要：

  We have previously demonstrated that conjugation of small molecule ligands to small interfering RNAs (siRNAs) and anti-microRNAs results in functional siRNAs and antagomirs in vivo. Here we report on the development of an efficient chemical strategy to make oligoribonucleotide-ligand conjugates using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) or click reaction. Three click reaction approaches were evaluated for their feasibility and suitability for high-throughput synthesis: the CuAAC reaction at the monomer level prior to oligonucleotide synthesis, the solution-phase postsynthetic "click conjugation", and the "click conjugation" on an immobilized and cornpletely protected alkyne-oligonucleotide scaffold. Nucleosides bearing 5'-alkyne moieties were used for conjugation to the 5'-end of the oligonucleotide. Previously described 2'- and 3'-O-propargylated nucleosides were prepared to introduce the alkyne moiety to the 3' and 5' termini and to the internal positions of the scaffold. Azido-functionalized ligands bearing lipophilic long chain alkyls, cholesterol, oligoamine, and carbohydrate were utilized to study the effect of physicochemical characteristics of the incoming azide on click conjugation to the alkyne-oligonucleotide scaffold in solution and on immobilized solid support. We found that microwave-assisted click conjugation of azido-functionalized ligands to a fully protected solid-support bound alkyne-oligonucleotide prior to deprotection was the most efficient "click conjugation" strategy for site-specific, high-throughput oligonucleotide conjugate synthesis tested. The siRNA conjugates synthesized using this approach effectively silenced expression of a luciferase gene in a stably transformed HeLa cell line.

  DOI：

  10.1021/jo101761g
• 作为产物：
  描述：

  2’,3’邻异亚丙基尿苷 在 吡啶 、 tetrakis(actonitrile)copper(I) hexafluorophosphate 、 水 、 铜 、 silver nitrate 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 74.0h， 生成 [(2R,3R,4R,5R,6R)-5-acetamido-3,4-diacetyloxy-6-[2-[2-[4-[[[(2R,3R,4R,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-(2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxycarbonylamino]methyl]triazol-1-yl]ethoxy]ethoxy]oxan-2-yl]methyl acetate
  参考文献：
  名称：

  Versatile Site-Specific Conjugation of Small Molecules to siRNA Using Click Chemistry

  摘要：

  We have previously demonstrated that conjugation of small molecule ligands to small interfering RNAs (siRNAs) and anti-microRNAs results in functional siRNAs and antagomirs in vivo. Here we report on the development of an efficient chemical strategy to make oligoribonucleotide-ligand conjugates using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) or click reaction. Three click reaction approaches were evaluated for their feasibility and suitability for high-throughput synthesis: the CuAAC reaction at the monomer level prior to oligonucleotide synthesis, the solution-phase postsynthetic "click conjugation", and the "click conjugation" on an immobilized and cornpletely protected alkyne-oligonucleotide scaffold. Nucleosides bearing 5'-alkyne moieties were used for conjugation to the 5'-end of the oligonucleotide. Previously described 2'- and 3'-O-propargylated nucleosides were prepared to introduce the alkyne moiety to the 3' and 5' termini and to the internal positions of the scaffold. Azido-functionalized ligands bearing lipophilic long chain alkyls, cholesterol, oligoamine, and carbohydrate were utilized to study the effect of physicochemical characteristics of the incoming azide on click conjugation to the alkyne-oligonucleotide scaffold in solution and on immobilized solid support. We found that microwave-assisted click conjugation of azido-functionalized ligands to a fully protected solid-support bound alkyne-oligonucleotide prior to deprotection was the most efficient "click conjugation" strategy for site-specific, high-throughput oligonucleotide conjugate synthesis tested. The siRNA conjugates synthesized using this approach effectively silenced expression of a luciferase gene in a stably transformed HeLa cell line.

  DOI：

  10.1021/jo101761g