Development of new debenzylative cyclization reactions and de novo synthesis of difluorinated glycomimetics

PhD thesis defended by Julien DELBROUCK (Prof. Stéphane VINCENT) - 20/11/2018

Prof. Stéphane VINCENT, UNamur, Laboratory of Bio-Organic Chemistry (CBO)


Matthieu SOLLOGOUB (Sorbonne Université), Michael SINGLETON (UCL), Guillaume BERIONNI (UNamur), Steve LANNERS (UNamur), président, Stéphane VINCENT (UNamur), promoteur


The first project of this thesis is dedicated to the study and the development of new debenzylative cyclization reactions to construct five-membered ring glycomimetics with various applications in bio-organic chemistry. Although benzyl ether constitutes a major class of protecting groups, debenzylative cyclization may occurs when a 1,4-relationship exist between an electrophilic center and a benzyl ether, to yield a tetrahydrofuran unit. The cyclization is highly stereo- and regio-selective in favor of five-membered ring over the tetrahydropyran isomer, thus suppressing the need of protecting group manipulation to ensure regioselective cyclization.

The second project deals with the multi-step synthesis of difluorinated substrate analogues of UDP-Galactopyranose Mutase (UGM). This enzyme is involved in the biosynthesis of the bacteria cell-wall of mycobacterium tuberculosis, the causative agent of tuberculosis (TB). Despite the availability of treatments, TB still remains a major threat for public health, mainly due to the emergence of multidrug resistant strains.