[(2R,3R,4R,5R)-4-[tert-butyl(dimethyl)silyl]oxy-3-[2-cyanoethoxy-[di(propan-2-yl)amino]phosphanyl]oxy-5-(2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl N-prop-2-ynylcarbamate | 1268341-98-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: [(2R,3R,4R,5R)-4-[tert-butyl(dimethyl)silyl]oxy-3-[2-cyanoethoxy-[di(propan-2-yl)amino]phosphanyl]oxy-5-(2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl N-prop-2-ynylcarbamate
• CAS: 1268341-98-5
• 化学式: C₂₈H₄₆N₅O₈PSi
• 分子量: 639.761
• InChiKey: AQGCCRVKFNGKFW-CMZUPCIYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.84
• 重原子数：
  43
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  152
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2’,3’邻异亚丙基尿苷 在 吡啶 、 水 、 silver nitrate 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 62.0h， 生成 [(2R,3R,4R,5R)-4-[tert-butyl(dimethyl)silyl]oxy-3-[2-cyanoethoxy-[di(propan-2-yl)amino]phosphanyl]oxy-5-(2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl N-prop-2-ynylcarbamate
  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

文献信息

• Versatile Site-Specific Conjugation of Small Molecules to siRNA Using Click Chemistry
  作者：Takeshi Yamada、Chang Geng Peng、Shigeo Matsuda、Haripriya Addepalli、K. Narayanannair Jayaprakash、Md. Rowshon Alam、Kathy Mills、Martin A. Maier、Klaus Charisse、Mitsuo Sekine、Muthiah Manoharan、Kallanthottathil G. Rajeev

  DOI：10.1021/jo101761g

  日期：2011.3.4

  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.