Synthesis of new quaternarized C-nucleoside analogues at the anomeric position as potential antiviral agents

The Health Academic Division of Euromed University of Fes organized a conference on the theme of "nucleosides," led by Professor Jacques Lebreton, a teacher at the University of Nantes, in the presence of Prof. Gérald Guillaumet, former president of the University of Orléans. This conference took place at the Euromed University of Fes eco-campus in the presence of students from the Health Academic Division and specialist professor-researchers in the field.

Note on the conference theme:

Nucleosides are involved in all phases of cell cycle regulation. Consequently, synthetic analogues, mimicking them and borrowing the same metabolic pathways, have led to therapeutic successes in the treatment of certain cancers and viral pathologies. Since the 1960s, about forty nucleoside analogues have been marketed for the treatment of cancerous and viral pathologies (nearly half of current antivirals are nucleoside analogues). The current pandemic linked to SARS-CoV-2 (COVID-19) illustrates the need to have effective and selective antivirals to combat these emerging pathogens.^1,2

In this context, C-nucleosides are nucleoside analogues whose C-N glycosidic bond has been replaced by a C-C bond, making them more stable against acid and enzymatic hydrolysis. Remdesivir (RDV) developed by Gilead laboratories is undoubtedly one of the most promising C-nucleosides, given its broad spectrum of activity against viruses such as yellow fever, dengue, or Ebola. Remdesivir even, for a time, brought a glimmer of hope in the fight against COVID-19.³

During recent work, carried out in collaboration with Janssen laboratories, we have developed a new route of access to new quaternized C-nucleoside analogues at the anomeric position with a cyano function, analogues of Remdesivir (RDV).⁴

1- D. L. Hughes. Org. Process Res. Dev. 2021, 25, 1089-1111 and references cited.

2-J. Lebreton. Nucleoside analogues for the treatment of coronavirus infections: an overview of their chemistry. AtlanChimPharma Scientific Letter (http://www.atlanchimpharma.com/our-scientific-letters/), 14, June, 2020 and references cited.

3-D. Mi. Tit et al. Biomed. Pharmacother. 2022, 147, 112700 (https://doi.org/10.1016/j.biopha.2022.112700) and references cited.

4-P. Sierocki, K. Gaillard, R. Arturo Arellano Reyes, C. Donnart, E. Lambert, S. Grosse, L. Arzel, A. Tessier, J. Guillemont, M. Mathé-Allainmat, J. Lebreton. Org. Biomol. Chem. 2022, 20, 2715-2728.

Jacques Lebreton

Nantes Université, CNRS, Laboratoire CEISAM-UMR6230, Faculté des Sciences et des Techniques, 2 rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France.

E-mail: jacques.lebreton@univ-nantes.fr