3'-O-acetyl-2'-O-methyluridine | 287101-01-3

• 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: 3'-O-acetyl-2'-O-methyluridine
• 英文别名: [(2R,3R,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-2-(hydroxymethyl)-4-methoxyoxolan-3-yl] acetate
• CAS: 287101-01-3
• 化学式: C₁₂H₁₆N₂O₇
• 分子量: 300.268
• InChiKey: UKAFETXWAJXXAI-QCNRFFRDSA-N

物化性质

• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3'-O-acetyl-2'-O-methyluridine 在 palladium on activated charcoal copper(l) iodide 、 四(三苯基膦)钯 、 氢气 、 一氯化碘 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 生成 3'-O-acetyl-5-(hydroxypropyl)-2'-O-methyluridine
  参考文献：
  名称：

  掺入在5′-末端位点具有环状结构的构象刚性尿苷单元的寡脱氧核苷酸的合成和性质。

  摘要：

  合成具有在尿嘧啶残基的5位和5'-磷酸基团之间连接的环状结构的2'-O-甲基尿苷酸衍生物3。NMR分析表明，该环尿苷酸衍生物仅具有C3'-endo构象，有利于与RNA形成双链体。通过在固相中使用完全保护的环尿苷酸3'-亚磷酰胺衍生物11，合成了两个在5'-末端位带有该环尿苷酸单元的寡核苷酸pc3Um（pT）（9）和pc3Um（pU）（9）。合成。为了检查这种环状结构对修饰寡核苷酸及其互补寡核苷酸之间双链体热稳定性的实际影响，还合成了具有无环结构的两个寡核苷酸——pUm（pT）（9）和pUm（pU）（9）。作为互补寡核苷酸，将dA（pdA）（9）和A（pA）（9）用于这些5'末端修饰寡核苷酸的T（m）实验。测量所有可能的双链体的T（m）值。这些结果清楚地表明，pc3Um（pT）（9）-A（pA）（9）的双链体比A（pA）（9）-T（pT）的T（m）值高5.5摄氏度。 （9）。与所有其他情况相

  DOI：

  10.1021/jo991374h
• 作为产物：
  描述：

  2'-甲氧基尿苷 在 咪唑 、 四丁基氟化铵 、 溶剂黄146 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 3'-O-acetyl-2'-O-methyluridine
  参考文献：
  名称：

  α-羟基-1,2,3-三唑连接的唾液酸转移酶抑制剂的合成和对 ST3GAL1、ST6GAL1 和 ST8SIA2 的选择性评价

  摘要：

  基于我们之前对 1,2,3-三唑连接的唾液酸转移酶抑制剂的研究，我们提出了一系列新化合物的设计和合成，这些化合物改进了母体支架的药物相似性。此外，我们还使用 STs hST3GAL1 、 hST6GAL1 和 hST8SIA2 进行了初步 SAR 研究。这项工作为选择性 ST 抑制剂的设计提供了新的见解，特别是考虑了不同的核苷衍生物。

  DOI：

  10.1002/cmdc.202400088

文献信息

• Stabilized siRNAs as transfection controls and silencing reagents
  申请人：Leake Devin

  公开号：US20070269889A1

  公开（公告）日：2007-11-22

  RNA molecules, including siRNA molecules and related control, trackability and exaequo agents with specific stability modifications are provided. These molecules are particularly advantageous as transfection control reagents. The molecules include first and second 5′ terminal sense nucleotides with 2′-O-alkyl groups and a label on the first 5′ terminal sense nucleotide, in conjunction with at least one additional 2′-O-alkyl pyrimidine modified sense nucleotide, and either: (i) at least one 2′ fluoro modified pyrimidine antisense nucleotide and a phosphorylated first 5′ terminal antisense nucleotide; or (ii) a first and second 5′ terminal antisense nucleotide with 2′-O-alkyl modifications and at least one additional 2′-O-alkyl pyrimidine modified antisense nucleotide.

  提供了包括siRNA分子和相关的控制、可追踪性和稳定性修饰的分子。这些分子作为转染控制试剂特别有优势。这些分子包括第一和第二个5'端感受核苷酸，具有2'-O-烷基基团和第一个5'端感受核苷酸上的标记，与至少一个额外的2'-O-烷基嘧啶修饰的感受核苷酸一起，以及：（i）至少一个2'-氟修饰的嘧啶反义核苷酸和一个磷酸化的第一个5'端反义核苷酸；或者（ii）第一和第二个5'端反义核苷酸具有2'-O-烷基修饰和至少一个额外的2'-O-烷基嘧啶修饰的反义核苷酸。
• STABILIZED SIRNAS AS TRANSFECTION CONTROLS AND SILENCING REAGENTS
  申请人：Leake Devin

  公开号：US20090280567A1

  公开（公告）日：2009-11-12

  RNA molecules, including siRNA molecules and related control, trackability and exaequo agents with specific stability modifications are provided. These molecules are particularly advantageous as transfection control reagents. The molecules include first and second 5′ terminal sense nucleotides with 2′-O-alkyl groups and a label on the first 5′ terminal sense nucleotide, in conjunction with at least one additional 2′-O-alkyl pyrimidine modified sense nucleotide, and either: (i) at least one 2′ fluoro modified pyrimidine antisense nucleotide and a phosphorylated first 5′ terminal antisense nucleotide; or (ii) a first and second 5′ terminal antisense nucleotide with 2′-O-alkyl modifications and at least one additional 2′-O-alkyl pyrimidine modified antisense nucleotide.

  提供了RNA分子，包括siRNA分子和相关的控制、可追踪性和具有特定稳定性修饰的exaequo剂。这些分子作为转染控制试剂特别有优势。这些分子包括第一和第二个5'端的感知核苷酸，具有2'-O-烷基基团和第一5'端的标签，以及至少一个附加的2'-O-烷基嘧啶修饰感知核苷酸，以及：(i)至少一个2'-氟修饰的嘧啶反义核苷酸和一个磷酸化的第一5'端反义核苷酸；或者(ii)第一和第二个5'端反义核苷酸具有2'-O-烷基修饰和至少一个附加的2'-O-烷基嘧啶修饰反义核苷酸。
• Stabilized RNAS as transfection controls and silencing reagents
  申请人：Dharmacon, Inc.

  公开号：EP2123759A2

  公开（公告）日：2009-11-25

  RNA molecules, including siRNA molecules and related control, trackability and exaequo agents with specific stability modifications are provided. These molecules are particularly advantageous as transfection control reagents. The molecules include an RNA duplex comprising: (a) a sense strand, wherein said sense strand comprises (i) a first 5' terminal sense nucleotide and a second 5' terminal sense nucleotide, wherein said first 5' terminal sense nucleotide comprises a first 2'-O-alkyl sense modification and said second 5' terminal sense nucleotide comprises a second 2'-O-alkyl sense modification; (ii) at least one 2'-O-alkyl pyrimidine modified sense nucleotide, wherein said at least one 2'-O-alkyl pyrimidine modified sense nucleotide is a nucleotide other than said first 5' terminal sense nucleotide or said second 5' terminal sense nucleotide; and (b) an antisense strand, wherein said antisense strand comprises (i) a first 5' terminal antisense nucleotide and a second 5' terminal antisense nucleotide, wherein said first 5' terminal antisense nucleotide comprises a first 2'-O-alkyl antisense modification and said second 5' terminal antisense nucleotide comprises a second 2'-O-alkyl antisense modification; and (ii) at least one 2'-O-alkyl pyrimidine modified antisense nucleotide, wherein said at least one 2'-O-alkyl modified antisense nucleotide is a nucleotide other than said first 5' terminal antisense nucleotide or said second 5' terminal antisense nucleotide, wherein the sense strand and antisense strand are capable of forming a duplex of between 16 and 50 base pairs.

  提供了包括 siRNA 分子在内的 RNA 分子以及具有特定稳定性修饰的相关控制、可追踪性和 exaequo 剂。这些分子作为转染控制试剂尤其具有优势。这些分子包括一个 RNA 双链，其中包括 (a) 有义链，其中所述有义链包括 (i) 第一个 5'末端有义核苷酸和第二个 5'末端有义核苷酸，其中所述第一个 5'末端有义核苷酸包括第一个 2'-O-烷基有义修饰，所述第二个 5'末端有义核苷酸包括第二个 2'-O-烷基有义修饰； (ii) 至少一个 2'-O-烷基嘧啶修饰的感应核苷酸，其中所述至少一个 2'-O-烷基嘧啶修饰的感应核苷酸是除所述第一 5'末端感应核苷酸或所述第二 5'末端感应核苷酸之外的核苷酸；以及 (b) 反义链，其中所述反义链包括 (i) 第一 5'末端反义核苷酸和第二 5'末端反义核苷酸，其中所述第一 5'末端反义核苷酸包括第一 2'-O-烷基反义修饰，所述第二 5'末端反义核苷酸包括第二 2'-O-烷基反义修饰；以及 (ii) 至少一个 2'-O-烷基嘧啶修饰的反义核苷酸，其中所述至少一个 2'-O-烷基修饰的反义核苷酸是所述第一 5'末端反义核苷酸或所述第二 5'末端反义核苷酸以外的核苷酸、 其中，有义链和反义链能够形成 16 至 50 个碱基对的双链。
• 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.
• Activity of siRNAs with 2-Thio-2′-<i>O</i>-Methyluridine Modification in Mammalian Cells
  作者：Thazha P. Prakash、Nishant Naik、Namir Sioufi、Balkrishen Bhat、Eric E. Swayze

  DOI：10.1080/15257770903316145

  日期：2009.10.28

  In a search to identify chemical modifications to improve the properties of siRNA, we ham investigated the effect of the 2'-O-methyl-2-thiouridine modification on the biological activity of siRNA. Our results indicate that judicious placement of 2'-O-methyl-thiouridine residues could lead to modified siRNA with activity in mammalian cells.