Our team is devoted to the synthesis of biologically active compounds (antioxidants compounds, antibiotics) and tools for biological studies (Imaging, complexation of cations, complexation of anions, synthetic multivalent platforms). The properties of the prepared compounds are evaluated in collaboration with biologists from the CEA or other research agencies. New synthetic methods are developed to carry out these projects.

Managers

Marie-Pierre HECK
marie-pierre.heck@cea.fr

Thierry LE GALL
thierry.legall@cea.fr

 
The team ©CEA/MP. Heck-T. Le Gall

Research projects of Marie-Pierre Heck

Synthesis and study of new cucurbiturils

Cucurbiturils, CB[n], are synthetic crown-shaped oligomers with a hydrophobic cavity accessible by two carbonyl portals that confer them properties of supramolecular recognition of "host-guest" type.

Despite the importance of gases in environment, science and medicine, their molecular recognition, especially in water, is not well documented. Interested in the encapsulation of rare gases and small alkanes in water, we have designed and synthesized a water-soluble cucurbiturils family, called CynCB[6] which have cyclohexyl units (n = 1-6). We have shown that the presence of one cyclohexyl group is sufficient to confer to these macrocycles a good solubility in water. After functionalization, they should be particularly interesting as xenon biosensors, able to image tissues and organs.

New unsaturated bambusurils

Bambusurils,BU[n], is a new family of synthetic macrocyclic whose first members were discovered in 2010. They differ from the CB[n] by their functionalized glycoluril units giving them a more flexible alternated structure and an internal cavity able to encapsulate anions. The latter, especially iodides, play important roles in biology and medicine. Having specific receptors is necessary to follow the path of anions, to measure and/or to extract them, and to understand their coordination. New bambusurils, allyl₈BU[4] and allyl₁₂BU[6] bearing alkenes, have been prepared by a new method using microwaves. They can be functionalized by cross-metathesis reaction, and important applications of these bambusurils as multivalent platforms of interest for complexation of iodides in the medical field can be envisaged.

Development of metathesis catalysts

As a part of a collaborative European project called Metacode (Code-engineered new-to-nature microbial cell factories for novel and safety-enhanced bio-production), the metathesis reaction is studied to be used in biological media to allow its use as an orthogonal reaction in synthetic biology.

Research projects of Thierry Le Gall

Synthesis of toxic metal complexing agents

Synthesis of the antibiotic ripostatin A

Over the past years, bacterial resistance has risen, making certain antibiotics inefficient. In this context, it is interesting to be able to identify new antibiotics, especially if they act according to original mechanisms of action. We are currently investigating the synthesis of ripostatin A, isolated from Sorangium cellulosum, which is an inhibitor of bacterial RNA polymerase, acting in an unusual way. Analogues will be evaluated as antibiotics.