Description of the thesis topic

Recruited by the CNRS within the IC2MP (Institut de Chimie des Milieux et Matériaux de Poitiers) and in collaboration with the BioCIS laboratory (Université de Cergy, France), the candidate will work on a project funded by the Agence Nationale de la Recherche (ANR-24-CE07-Sweet_N_Fun).
Glycomimetics are key compounds in the search for new diagnostic and therapeutic targets. They offer the possibility of mimicking the activities of carbohydrates while circumventing their drawbacks as drug candidates. Iminosugars are among the most promising glycomimetics, as illustrated by the FDA approval of three drugs (miglustat, miglitol, migalastat) to treat diabetes and rare diseases (Gaucher, Pompe, Fabry, Niemann-Pick). These molecules generally act as inhibitors of glycosidases (GH) and glycosyltransferases (GT) by mimicking the oxocarbenium ion character of their transition state. To date, their chemical modulation at positions that do not interfere with enzyme recognition, namely the intracyclic nitrogen atom to obtain N-alkyl iminoalditols and the pseudoanomeric position to obtain C-glycoside iminosugars, has been achieved to improve both their inhibition capacity and selectivity. The modification of other iminosugar ring positions has been little studied, despite promising results. Selective modulation of the C1 and C2 positions of iminosugars is the objective of this project, which requires both suitable precursors and efficient methodologies to introduce molecular diversity in a regio- and stereoselective manner. Iminoglycals, little-studied mimetics of glycals bearing an enamine function, are ideal precursors for this study. The aim of this project is to expand the chemical space of iminosugars by combining the chemistry of underexplored sugar derivatives, iminoglycals, with metal-catalyzed coupling methodologies, to produce novel glycomimetics whose biological potential will be assessed by a network of collaborators.
In this context, the candidate recruited will be in charge of the design, synthesis and characterization of new glycomimetics.
The candidate will be responsible for the following activities:
- Design and multi-step synthesis of novel iminoglycals and glycomimetics.
- Development of metallo-catalyzed reactions.
- Purification and characterization of synthesized compounds (NMR, HRMS, HPLC).
- Presentation of results at consortium progress meetings.
- Preparation of reports (bibliographical and progress reports).
Expected skills:
- The candidate must have excellent skills in organic chemistry (Master II level). Skills in glycochemistry and/or organocatalysis will be appreciated.
- The candidate must master the techniques of classical synthesis and analysis of organic molecules.
- The candidate must have a good level of written/oral English.
- Good writing skills (French/English).
- The candidate must be able to work independently and as part of a team.

Work Context

Recruited by the CNRS, the PhD student will work in the Organic Synthesis team at the Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP - https://ic2mp.labo.univ-poitiers.fr/).
He/she will work in the Glycochimie group, which has strong expertise in the synthesis of sugar mimes targeting glycoenzymes.

Constraints and risks

Standard chemical hazards.
The candidate will be subject to the laboratory's internal rules for all health and safety regulations.
Occasional assignments in France or abroad are possible.