AUTHOR=Naciuk Fabrício Fredo , Nascimento Andrey Fabricio Ziem , Rocha Rebeca Paiva Froes , Rustiguel Joane Kathelen , Coimbra Lais Durço , Marques Rafael Elias , Bruder Marjorie TITLE=Competing interests during the key N-glycosylation of 6-chloro-7-deaza-7-iodopurine for the synthesis of 7-deaza-2′-methyladenosine using Vorbrüggen conditions JOURNAL=Frontiers in Chemistry VOLUME=11 YEAR=2023 URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2023.1163486 DOI=10.3389/fchem.2023.1163486 ISSN=2296-2646 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 N-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 in vitro.