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

UEMF's health division organized a lecture on the topic of "nucleosides", led by Professor Jacques Lebreton, lecturer at the University of Nantes, in the presence of Prof. Gérald Guillaumet, former president of the University of Orléans. This lecture took place on UEMF's eco-campus in the presence of health division students and specialist research professors. 

 

Note sur la thématique de la conférence : 

 

Nucleosides are involved in all phases of cell cycle regulation. Indeed, synthetic analogues that mimic these molecules and follow the same metabolic pathways have led to therapeutic successes for the treatment of certain cancers and viral diseases. Since the 60s, around forty nucleoside analogues have been marketed for the treatment of cancerous and viral pathologies (nearly half of current antivirals are nucleoside analogues). The current SARS-CoV-2 (COVID-19) pandemic illustrates the need to have effective and selective antivirals to combat these emerging pathogens.^1,2

Dans ce cadre, Les CC-nucleosides are nucleoside analogues whose glycosidic C-N bond has been replaced by a C-C bond, making them more stable against acid and enzymatic hydrolysis. Remdesivir (RDV) developed by the Gilead laboratories is probably one of the Cmost promising C-nucleosides, given its broad spectrum of activity against viruses such as yellow fever, dengue or Ebola. Remdesivir even briefly offered a glimmer of hope in the fight against COVID-19.³

In recent work, carried out in collaboration with the Janssen laboratories, we developed a new route to access new Cquaternized 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 et références citées.

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 et références citées.

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

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, CEISAM Laboratory-UMR6230, Faculty of Science and Technology, 2 rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France.

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