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

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.

Phenotypical Screening of an MMV Open Box Library and Identification of Compounds with Antiviral Activity against St. Louis Encephalitis Virus

“…The MMV COVID Box library compounds were screened at final concentrations of 20 µM. Additionally, the flaviviral polymerase inhibitor 7-deaza-2 -C-methyladenosine (7DMA) was included within the set of compounds as a treatment positive control for CPE inhibition, due to its reported antiviral activity against other flaviviruses [20,21]. Cell cultures were infected with SLEV at an MOI of 0.5 shortly after the addition of compounds and incubated for 72 h. Afterward, fixed and stained cell cultures were analyzed using a high-content microscope to quantify living cells through nuclei counting.…”