[(2R,3R,4R,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-(2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methyl N-[[1-[(9Z,12Z)-octadeca-9,12-dienyl]triazol-4-yl]methyl]carbamate | 1268342-14-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: [(2R,3R,4R,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-(2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methyl N-[[1-[(9Z,12Z)-octadeca-9,12-dienyl]triazol-4-yl]methyl]carbamate
• CAS: 1268342-14-8
• 化学式: C₃₇H₆₂N₆O₇Si
• 分子量: 731.021
• InChiKey: MIABPYKSUHHKQN-RDOWAUALSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.52
• 重原子数：
  51
• 可旋转键数：
  24
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  157
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  [(2R,3R,4R,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-(2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methyl N-[[1-[(9Z,12Z)-octadeca-9,12-dienyl]triazol-4-yl]methyl]carbamate 、 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50%的产率得到[(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-[[1-[(9Z,12Z)-octadeca-9,12-dienyl]triazol-4-yl]methyl]carbamate
  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：

  亚麻醇 在 sodium azide 、 tetrakis(actonitrile)copper(I) hexafluorophosphate 、 铜 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.0h， 生成 [(2R,3R,4R,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-(2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methyl N-[[1-[(9Z,12Z)-octadeca-9,12-dienyl]triazol-4-yl]methyl]carbamate
  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.