Reference : UPR2301-JEABET-004
Workplace : GIF SUR YVETTE
Date of publication : Wednesday, May 11, 2022
Scientific Responsible name : Jean-Francois BETZER
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 October 2022
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
In 2017 at the ICSN (Institut de Chimie des Substances Naturelles), an institute dedicated to fundamental and applied research on natural products, the team of Dr. J. Ouazzani (partner in this project) isolated a new natural compound EA-2801 from the fungus Trichoderma atroviridae which exhibiting antimicrobial activities, especially against Gram-negative bacteria. Synthetic studies have shown that the target skeleton of EA-2801, that means HHMCP (HydroxyHydroxyMethylCycloPentenone) could be obtained in a single step by Piancatelli rearrangements from unsymmetrical furan-2,5-dicarbinols (FDC).
These preliminary results will allow the extension of this synthetic approach in order to develop a general route to the substituted cyclopentenone target unit of the natural product. This synthetic approach will be applied to the synthesis of the natural product EA-2801, but also to the synthesis of synthetic analogues, nitrogen derivatives (aza-Piancatelli reaction) of the natural product EA-2801 and fused bicyclic compounds. In parallel to these synthetic works, the evaluation of the antimicrobial activities will be carried out on all the synthesized compounds, but also on all the synthetic intermediates (the biological tests will be carried out by the partner of this project). In a second step, asymmetric versions of this rearrangement, by organocatalysis or organometallic catalysis, will be developed.
The work will be carried out at ICSN (Institute of Chemistry of Natural Substances), in the department of Organic Synthesis and Catalytic Methods (SOMC) and more precisely in the group Chemistry of Phosphorus and Catalysis: https://icsn.cnrs.fr/recherche/SOMC/CPC. The activities of the laboratory are centered around the development of new tools for catalysis, the development of new synthetic methodologies and their synthetic applications.
The antimicrobial activities of the target compounds, but also of the synthetic intermediates, will be carried out in the Microbial Secondary Metabolites group led by Dr. Jamal OUAZZANI of the Department of Chemistry of Natural Substances and Medicinal Chemistry (SNCM) of ICSN: http://pilotunit.com/
Thus, this collaborative project will be carried out between two research teams of the ICSN, a CNRS research unit (UPR2301) which has been internationally recognized in organic and medicinal chemistry for several decades. The ICSN develops activities ranging from the discovery of new natural substances, to the research of their mechanisms of action, through the synthesis of these molecules and the development of new methodologies in organic synthesis.
The candidate will benefit from a particularly lively scientific life at ICSN within the department of Organic Synthesis and Catalytic Methods (SOMC)
Constraints and risks
Occupational risks inherent to research work in the field of chemistry.
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