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Chemical Triphosphorylation of Oligonucleotides
Published on: June 2, 2022
使用双循环酸衍生物作为单体单体的立体常规寡氧核核酸酸的固相合成
Natsuhisa Oka1, Mika Yamamoto, Terutoshi Sato
1Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Bioscience Building 702, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan.
Journal of the American Chemical Society
|November 5, 2008
概括
新的双循环氧化聚胺单体使得具有高二选择性的酸寡氧化核化物 (PS-ODN) 的立体控制的固相合成成为可能.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 生物化学 生物化学
背景情况:
- 固相合成对于制造DNA和RNA类似物至关重要.
- 酸酸链接是治疗性寡核酸的重要修改.
- 在合成过程中控制立体化学对于生物活动至关重要.
研究的目的:
- 开发新型单体单元,用于酸寡氧化核化物 (PS-ODN) 的立体选择性合成.
- 在合成过程中研究核酸3'-O-双循环酸衍生物的立体化学稳定性.
主要方法:
- 核酸3'-O-双循环酸衍生物的转异构体的合成.
- 使用酸性激活剂进行固体相凝结.
- 开始分子轨道计算以研究表皮化机制.
主要成果:
- 独家生成具有高 diastereopurity (>或=99:1) 的跨-oxazaphospholidine异构体.
- 在固体支上酸凝结过程中,跨异构体的稳定配置.
- 证明了 (Rp) - 和 (Sp) - 酸酸连接的形成,而不会损失 diastereopurity.
结论:
- 核酸3'-O-双循环氧酸衍生物是立体规律PS-ODN合成的有效单体.
- 通过对表皮化途径的计算分析,观察到的配置稳定性得到了合理化.
- 这种方法可以精确地控制酸核酸中核酸链接的立体化学.
相关概念视频
Phosphodiester Linkages
Overview
Phosphodiester bond forms when a phosphoric acid molecule (H3PO4) links with two hydroxyl groups (–OH) of two other molecules, forming two ester bonds. Two water molecules are released in this process. The phosphodiester bond is commonly found in nucleic acids (DNA and RNA) and plays a critical role in their structure and function.
Phosphodiester Bonds Link Nucleotides Together
DNA and RNA are polynucleotides or long chains of nucleotides that are linked together. A nucleotide is...
Phosphodiester bond forms when a phosphoric acid molecule (H3PO4) links with two hydroxyl groups (–OH) of two other molecules, forming two ester bonds. Two water molecules are released in this process. The phosphodiester bond is commonly found in nucleic acids (DNA and RNA) and plays a critical role in their structure and function.
Phosphodiester Bonds Link Nucleotides Together
DNA and RNA are polynucleotides or long chains of nucleotides that are linked together. A nucleotide is...
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Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...

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