Seminar of Yvan Guindon

“From Free Radicals and Glycochemistry to Novel Bioactives Molecules”


Yvan GUINDON

Université de Montréal

Friday 10th November 2023 à 11h

Sorbonne University
Pierre et Marie Curie Campus
Tower 24-34, room 105

Abstract:

Various unique and complementary methods for the synthesis of complex and biologically interesting molecules will be presented. New stereoselective methodologies involving free radicals are applied to the preparation of complex molecules such as polypropionates and stereogenic centres. Nucleoside analogues bearing a fully carbonated quaternary centre at C2′ or C3′ have been conceptualised and approaches to their synthesis are underway. To achieve these goals, various synthetic methodologies involving the development of highly diastereoselective acyclic pathways to construct each stereogenic centre are being developed; namely, a Mukaiyama aldol reaction, intramolecular radical atom cyclisation using photoredox catalysis, diastereoselective introduction of various C2′ substituents followed by selective N-glycosylations. The molecules are being evaluated for their antiviral, antitumour and cardioprotective effects. A series of new nucleoside analogues bearing a fully carbonated C2′ stereogenic centre is being developed for the treatment of acute and chronic heart failure. The lead compound’s cardioprotective effect has been observed in a variety of conditions known to lead to heart failure, including treatment with cardiotoxic agents, loss of survival genes and pressure overload.

The design and synthesis of selective selectin ligands that could be used as therapeutic agents to control inflammation is another research interest of the Guindon laboratory. Sialyl LewisX (sLeX) glycomimetics as E- and P-selectin antagonists are being developed for the treatment of vaso-occlusive crisis in sickle cell anaemia patients, cancer cell metastases and many serious lung infections such as acute lung injury and acute respiratory distress syndrome, two complications of Covid-19. A new series of sLex analogues in which the GlcNAc is replaced by an acyclic tether that imposes the necessary left-hand conformation between the fucoside and galactoside of sLeX has been developed. To improve on the first-generation scaffolds, the conformation of the Gal-C3 carboxylic acid moiety was restricted by the synthesis of fused bicyclo-3O, 4C galactopyranosides that control the conformation of the carboxylic acid moiety of the bicyclic ring. A new synthetic route allowed the introduction of various carboxylate bioisoters through the addition of equatorial propiolate nucleophiles and selective C-glycosylation reactions.

CV-Dr. Yvan Guindon

Contact IPCM :
Matthieu Sollogoub