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在使用Vorbrüggen条件合成7-脱氮-2'-甲基腺苷时，6-氯-7-脱氮-7-碘嘌呤关键糖基化过程中的竞争利益。

Competing interests during the key -glycosylation of 6-chloro-7-deaza-7-iodopurine for the synthesis of 7-deaza-2'-methyladenosine using Vorbrüggen conditions.

作者信息

Naciuk Fabrício Fredo, Nascimento Andrey Fabricio Ziem, Rocha Rebeca Paiva Froes, Rustiguel Joane Kathelen, Coimbra Lais Durço, Marques Rafael Elias, Bruder Marjorie

机构信息

Brazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, São Paulo, Brazil.

Brazilian Synchrotron Light Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, São Paulo, Brazil.

出版信息

Front Chem. 2023 Mar 23;11:1163486. doi: 10.3389/fchem.2023.1163486. eCollection 2023.

DOI:10.3389/fchem.2023.1163486
PMID:37035111
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10076608/
Abstract

A short 3-step synthesis of the antiviral agent 7DMA is described herein. The nature of a major by-product formed during the key -glycosylation of 6-chloro-7-deaza-7-iodopurine with perbenzoylated 2-methyl-ribose under Vorbrüggen conditions was also investigated. Spectroscopic analyses support that the solvent itself is converted into a nucleophilic species competing with the nucleobase and further reacting with the activated riboside in an unanticipated fashion. These findings call for a revision of reaction conditions when working with weakly reactive nucleobases in the presence of Lewis acids. 7DMA thus obtained was evaluated for its efficacy against an emerging flavivirus .

摘要

本文描述了抗病毒药物7DMA的简短三步合成法。还研究了在Vorbrüggen条件下，6-氯-7-脱氮-7-碘嘌呤与全苯甲酰化的2-甲基核糖进行关键的糖基化反应过程中形成的主要副产物的性质。光谱分析表明，溶剂本身转化为一种亲核物种，与核碱基竞争，并以一种意想不到的方式进一步与活化的核糖苷反应。这些发现要求在路易斯酸存在下使用弱反应性核碱基时对反应条件进行修正。由此获得的7DMA针对一种新出现的黄病毒进行了疗效评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c425/10076608/c36988a302fb/fchem-11-1163486-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c425/10076608/1ee27e9e6176/fchem-11-1163486-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c425/10076608/8e2a62a629e8/FCHEM_fchem-2023-1163486_wc_sch1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c425/10076608/778999dc9119/FCHEM_fchem-2023-1163486_wc_sch2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c425/10076608/5a19ddae26d8/fchem-11-1163486-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c425/10076608/7c80f75af216/fchem-11-1163486-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c425/10076608/826729045732/FCHEM_fchem-2023-1163486_wc_sch3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c425/10076608/ec452c7c2f99/FCHEM_fchem-2023-1163486_wc_sch4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c425/10076608/c36988a302fb/fchem-11-1163486-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c425/10076608/1ee27e9e6176/fchem-11-1163486-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c425/10076608/8e2a62a629e8/FCHEM_fchem-2023-1163486_wc_sch1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c425/10076608/778999dc9119/FCHEM_fchem-2023-1163486_wc_sch2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c425/10076608/5a19ddae26d8/fchem-11-1163486-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c425/10076608/7c80f75af216/fchem-11-1163486-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c425/10076608/826729045732/FCHEM_fchem-2023-1163486_wc_sch3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c425/10076608/ec452c7c2f99/FCHEM_fchem-2023-1163486_wc_sch4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c425/10076608/c36988a302fb/fchem-11-1163486-g004.jpg

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