5'-O-[bis((4-methoxyphenyl)phenylmethyl)-5-methyl-3'-O-2-propyn-1-yl]uridine | 1268342-11-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 5'-O-[bis((4-methoxyphenyl)phenylmethyl)-5-methyl-3'-O-2-propyn-1-yl]uridine
• 英文别名: 5'-O-(4,4'-dimethoxytrityl)-3'-O-propargyl-5-methyluridine；prop-2-ynyl(-3)[DMT(-5)]Ribf(b)-thymin-1-yl；1-[(2R,3R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3-hydroxy-4-prop-2-ynoxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 1268342-11-5
• 化学式: C₃₄H₃₄N₂O₈
• 分子量: 598.653
• InChiKey: MQIYRDLOXXMRBN-PBAMLIMUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  44
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-azido-docosane 、 5'-O-[bis((4-methoxyphenyl)phenylmethyl)-5-methyl-3'-O-2-propyn-1-yl]uridine 在 tris(triazolylmethyl)amine copper chelation complex 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 以99%的产率得到
  参考文献：
  名称：

  An immobilized and reusable Cu(i) catalyst for metal ion-free conjugation of ligands to fully deprotected oligonucleotides through click reaction

  摘要：

  将 Cu(I)离子与固定在固体载体上的亲水性三（三氮唑甲基）胺螯合剂螯合后，可利用完全脱保护的炔寡核苷酸合成 RNA 寡核苷酸共轭物。没有观察到寡核苷酸链降解或金属离子污染。此外，固定铜（I）离子的使用克服了与应变促进无铜叠氮-炔环加成相关的区域选择性问题。

  DOI：

  10.1039/c2cc36811k
• 作为产物：
  描述：

  3-氯丙炔 、 1-<5-O--β-D-ribofuranosyl>-5-methyl-1-1H,3H-pyrimidine-2,4-dione 在 四丁基碘化铵 、 二正丁基氧化锡 作用下， 以 乙腈 、 苯 为溶剂， 以40%的产率得到prop-2-ynyl(-2)[DMT(-5)]Ribf(b)-thymin-1-yl
  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

• Cross-Linked DNA: Propargylated Ribonucleosides as “Click” Ligation Sites for Bifunctional Azides
  作者：Suresh S. Pujari、Frank Seela

  DOI：10.1021/jo300421p

  日期：2012.5.4

  2'-O or 3'-O-propargylated adenosines and ribothymidines were used as click targets for cross-linking of oligonucleotides with aliphatic and aromatic azides. The cross-link generates a sugar modification at the 2'-O-ligation site. Inexpensive ribonucleosides were used as starting materials. Cross-linking of oligonucleotides was performed at internal or terminal positions. Hybridization of homodimers with two complementary single strands resulted in stable ligated DNA duplexes.
• 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.
• An immobilized and reusable Cu(<scp>i</scp>) catalyst for metal ion-free conjugation of ligands to fully deprotected oligonucleotides through click reaction
  作者：Laxman Eltepu、Muthusamy Jayaraman、Kallanthottathil G. Rajeev、Muthiah Manoharan

  DOI：10.1039/c2cc36811k

  日期：——

  Chelation of Cu(I) ions to an immobilized hydrophilic tris(triazolylmethyl)amine chelator on a solid support allowed synthesis of RNA oligonucleotide conjugates from completely deprotected alkyne-oligonucleotides. No oligonucleotide strand degradation or metal ion contamination was observed. Furthermore, use of the immobilized copper(I) ion overcame regioselectivity issues associated with strain-promoted copper-free azide–alkyne cycloaddition.

  将 Cu(I)离子与固定在固体载体上的亲水性三（三氮唑甲基）胺螯合剂螯合后，可利用完全脱保护的炔寡核苷酸合成 RNA 寡核苷酸共轭物。没有观察到寡核苷酸链降解或金属离子污染。此外，固定铜（I）离子的使用克服了与应变促进无铜叠氮-炔环加成相关的区域选择性问题。