An improved synthesis of guanosine TNA phosphoramidite for oligonucleotide synthesis.

IF 1.3 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Nucleosides, Nucleotides & Nucleic Acids Pub Date : 2025-01-01 Epub Date: 2024-06-21 DOI:10.1080/15257770.2024.2369688
Biju Majumdar, Daisy Sarma, Erica M Lee, Noah A Setterholm, John C Chaput
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Abstract

The chemical synthesis of guanosine nucleosides generates both the N9 and N7 regioisomers, which require careful separation to obtain the desired N9 isomer. To preferentially obtain the N9 isomer, a bulky diphenylcarbamoyl (DPC) group can be installed at the O6 position of guanine. However, installation of the DPC group presents a challenging task due to low solubility of the N-acetyl protected guanine. Here we report the usage of commercially available 2-amino-6-chloro purine as a new strategy that offers a more efficient route to the synthesis of the guanine phosphoramidite of threose nucleic acid (TNA).

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用于寡核苷酸合成的鸟苷 TNA 亚磷酰胺的改进合成法。
鸟苷核苷的化学合成会产生 N9 和 N7 两种异构体,需要仔细分离才能得到所需的 N9 异构体。为了优先获得 N9 异构体,可以在鸟嘌呤的 O6 位安装一个大体积的二苯基氨基甲酰基(DPC)。然而,由于 N-乙酰基保护鸟嘌呤的溶解度较低,安装 DPC 基团是一项具有挑战性的任务。在此,我们报告了使用市售的 2-氨基-6-氯嘌呤作为一种新策略,为合成苏氨酸核酸(TNA)的鸟嘌呤磷酰胺提供了一条更有效的途径。
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来源期刊
Nucleosides, Nucleotides & Nucleic Acids
Nucleosides, Nucleotides & Nucleic Acids 生物-生化与分子生物学
CiteScore
2.60
自引率
7.70%
发文量
91
审稿时长
6 months
期刊介绍: Nucleosides, Nucleotides & Nucleic Acids publishes research articles, short notices, and concise, critical reviews of related topics that focus on the chemistry and biology of nucleosides, nucleotides, and nucleic acids. Complete with experimental details, this all-inclusive journal emphasizes the synthesis, biological activities, new and improved synthetic methods, and significant observations related to new compounds.
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