2′-氟化北甲碳环(2′-F-NMC)核苷的合成及其与寡核苷酸的结合

Q4 Chemistry
Masaaki Akabane-Nakata, Pawan Kumar, Namrata D. Erande, Shigeo Matsuda, Muthiah Manoharan
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引用次数: 0

摘要

本文描述了基于含有所有四种天然核碱基(U, C, a和G)的双环[3.1.0]己烷支架的2 ' -氟化北方甲烷碳环(2 ' -F-NMC)核苷和磷酰胺的化学合成,并通过固体负载合成将其纳入寡核苷酸中。这种合成从市售的环戊烯-2-烯-1- 1开始,得到氟化碳环假糖中间体(S.13),它可以通过与异氰酸酯缩合,然后环化,转化为尿嘧啶中间体,并通过微波辅助反应转化为腺嘌呤和鸟嘌呤前体。所有四种2 ' -F-NMC磷酰胺都是由S.13以会聚法合成的,这些单体用于合成2 ' -F-NMC修饰的寡核苷酸。©2020 by John Wiley &基本方案1:制备氟化碳环假糖中间体基本方案2:制备2′-F-NMC尿苷和胞苷磷酸基基本方案3:制备2′-F-NMC腺苷磷酸基本方案4:制备2′-F-NMC鸟苷磷酸基本方案5:合成含有2′-F-NMC的寡核苷酸
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synthesis of 2′-Fluorinated Northern Methanocarbacyclic (2′-F-NMC) Nucleosides and Their Incorporation Into Oligonucleotides

This article describes chemical synthesis of 2′-fluorinated Northern methanocarbacyclic (2′-F-NMC) nucleosides and phosphoramidites, based on a bicyclo[3.1.0]hexane scaffold bearing all four natural nucleobases (U, C, A, and G), and their incorporation into oligonucleotides by solid-supported synthesis. This synthesis starts from commercially available cyclopent-2-en-1-one to obtain the fluorinated carbocyclic pseudosugar intermediate (S.13), which can be converted to the uridine intermediate by condensation with isocyanate, followed by cyclization, and to adenine and guanine precursors by microwave-assisted reactions. All four 2′-F-NMC phosphoramidites are synthesized from S.13 in a convergent approach, and the monomers are used for synthesis of 2′-F-NMC-modified oligonucleotides. © 2020 by John Wiley & Sons, Inc.

Basic Protocol 1: Preparation of fluorinated carbocyclic pseudosugar intermediate

Basic Protocol 2: Preparation of 2′-F-NMC uridine and cytidine phosphoramidites

Basic Protocol 3: Preparation of 2′-F-NMC adenosine phosphoramidite

Basic Protocol 4: Preparation of 2′-F-NMC guanosine phosphoramidite

Basic Protocol 5: Synthesis of oligonucleotides containing 2ʹ-F-NMC

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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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