Carbocyclic C-C Bond Formation: Intramolecular Radical Ring Closure to Yield Diastereomerically Pure (7′S-Me- or 7′R-Me-) Carba-LNA Nucleotide Analogs

Q4 Chemistry
Oleksandr Plashkevych, Ram Shankar Upadhayaya, Jyoti Chattopadhyaya
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引用次数: 0

Abstract

In light of the impressive gene-silencing properties of carba-LNA modified oligo DNA and RNA, both in antisense RNA and siRNA approaches, which have been confirmed as proof-of-concept for biochemical applications in post-transcriptional gene silencing, we envision the true potential of carba-LNA modifications to be revealed soon. Herein we provide detailed protocols for synthesis of carba-LNA-A, -G, -5-MeC, and -T nucleosides on a medium/large scale (gram scale), as well as important guidelines for incorporation of these modified carba-LNAs into DNA or RNA oligonucleotides. Creation of a stereoselective C-C bond during the 5-exo radical intramolecular cyclization involves trapping of a C2′ radical intermediate intramolecularly by the vicinal double bond of a C4′-tethered ─CH2-CH═CH2 group. All diastereomers of substituted carba-LNAs are now available in pure form. The present procedure allows carba-LNA to be commercialized for medicinal or biotechnological purposes. © 2017 by John Wiley & Sons, Inc.

碳环C-C键形成:分子内自由基环闭合产生非对映纯(7'S-Me -或7'R-Me -)碳- rna核苷酸类似物
鉴于carba-LNA修饰寡核苷酸和RNA的令人印象深刻的基因沉默特性,无论是反义RNA还是siRNA方法,都已被证实为生物化学在转录后基因沉默中的应用概念验证,我们设想carba-LNA修饰的真正潜力将很快被揭示。本文提供了中/大规模(克级)合成碳- lna - a、-G、-5-MeC和-T核苷的详细方案,以及将这些修饰的碳- lnas整合到DNA或RNA寡核苷酸中的重要指南。在5-外显子自由基分子内环化过程中,立体选择性C-C键的形成涉及到一个C2 '自由基中间分子内被一个C4 ' -拴在一起的CH2- ch = CH2基团的邻近双键捕获。取代碳- lnas的所有非对映体现在都有纯形式。本程序允许碳水化合物rna商业化用于医药或生物技术目的。©2017 by John Wiley &儿子,Inc。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current Protocols in Nucleic Acid Chemistry
Current Protocols in Nucleic Acid Chemistry Chemistry-Organic Chemistry
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期刊介绍: Published in association with International Society for Nucleosides, Nucleotides & Nucleic Acids (IS3NA) , Current Protocols in Nucleic Acid Chemistry is equally valuable for biotech, pharmaceutical, and academic labs. It is the resource for designing and running successful research projects in the rapidly growing and changing field of nucleic acid, nucleotide, and nucleoside research.
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