Synthesis of novel quaternized C-nucleoside analogs in anomeric position as potential antiviral agents
Conference cycle
The UEMF health center organized a conference, around the theme of "nucleosides", moderated by Professor Jacques Lebreton, teacher at the University of Nantes, in the presence of Professor Gérald Guillaumet, former president of the University of Orléans. This conference took place in the UEMF eco-campus in the presence of students from the health center and professors and researchers specializing in the subject.
Note on the theme of the conference:
Nucleosides are involved in all phases of cell cycle regulation. In fact, synthetic analogues, mimicking the latter and following the same metabolic pathways, have led to therapeutic successes for the treatment of certain cancers and viral pathologies. Since the 1960s, around forty nucleoside analogues have been put on the market for the treatment of cancer and viral pathologies (nearly half of current antivirals are nucleoside analogues). The current pandemic linked to SARS-CoV-2 (COVID-19) illustrates the need for effective and selective antivirals to combat these emerging pathogens. 1,2
In this context, C -nucleosides are nucleoside analogues whose CN glycoside bond has been replaced by a CC bond, making them more stable with respect to acid and enzymatic hydrolysis. Remdesevir (RDV) developed by Gilead laboratories is undoubtedly one of the C -nucleosides, given its broad spectrum of activity on viruses such as yellow fever, dengue or Ebola. Remdesivir, for a time, even 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 to access new C -nucleoside analogues in an anomeric position with a cyano function, analogues of Remdesevir (RDV). 4
1- DL Hughes. Org. Process Res. Dev . 2021 , 25 , 1089-1111 and references cited.
2-J. Breton. 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 University, CNRS, CEISAM-UMR6230 Laboratory, Faculty of Sciences and Technology, 2 rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France.
E-mail: jacques.lebreton@univ-nantes.fr
