The IMPHOCHEM project deals with photochemical transformations of cyclic imines, which is based on a multidisciplinary approach combining organic synthesis, theoretical chemistry and chemical engineering. In this reactions, after photochemical excitation, an intramolecular hydrogen transfer occurs from the hydrogen donor moiety to the electronically excited imine function, involving thus a C H activation without a chemical regent. In the context of the project, two principal mechanisms are discussed: the hydrogen atom is transferred in one-step process (the proton and the electron are simultaneously transferred) or a two-step process takes place (the electron is transferred first and the proton follows). Depending on the hydrogen donor and the substitution of the imine, one of these mechanisms is preferred. After radical combination, a C C or a C N bond is formed. Different stereoisomers are formed. Particular attention is paid to the influence of the mechanism and the temperature on the stereo and regioselectivity. Theoretical methods are used in order to determine the properties of the excited state (spin density, electron distribution) and to study conformational equilibria. In the case of a two-step mechanism of hydrogen transfer involving photochemical electron transfer, photoredox catalysis (with visible light) is possible. Corresponding reaction conditions will be tested. In order to determine scope and limitation of the reaction, the substitution of the imine and the nature of the hydrogen donor will be broadly varied. Natural product derived structures (for example: carbohydrates, alkaloids or steroids) will also be attached as hydrogen donor. These variations will lead to an original molecular complexity and a high molecular diversity. A certain number of particularly efficient and original reactions will be selected in order to prove their usefulness for application to organic synthesis, more precisely for the synthesis of biologically active compounds. The study of photochemical transformations under flux conditions is a further original point of the project. A LED-driven microreactor operating in the UV-B domain (below 300 nm) and under temperature-controlled condition will be used. The conception and construction of such a reactor is particularly challenging and will open numerous perspectives in the field of flow photochemistry. Using such a reactor in this project will also help to understand fundamental aspects on how the selectivity depends on the temperature and the irradiation. By combining specific experiments with the modeling tools of photochemical reactor engineering, it will be possible to define the optimal operating conditions and to evaluate the feasibility of a transposition to a larger scale.

Among the numerous chiral auxiliaries which are available, N-tert-butanesulfinamides developed by Ellman have been increasingly used for the preparation of a wide range of chiral mono- and poly-functionalized amines derivatives. In spite of the obvious interesting properties of Ellman’s auxiliary such as its high-level reactivity, the availability of both enantiomers and the mild conditions required for its cleavage, the alkyl(aryl) trifluoromethyl-substituted N-tert-butanesulfinyl ketoimines have been under-used due to their high instability. As perfluoroalkyl groups adjacent to imines are known to increase their reactivity towards nucleophiles and to have a stabilizing effect for the obtained quaternary species, we recently reported the synthesis of the bench-stable N-tert-butanesulfinyl alpha-alkyl(aryl) alpha-trifluoromethyl hemiaminals as surrogates of the corresponding ketoimines. We thus propose to develop the short and scalable asymmetric syntheses of a variety of compounds containing a quaternary trifluoromethyl group adjacent to a nitrogen atom by addition of nucleophiles on these stable analogues of chiral imines. Among them, enantiopure trifluoromethylated beta3,3-amino acids will be used as fragments for the elaboration of a set of heterogeneous alpha/beta- and homogeneous beta-peptides which secondary structures will be further determined in solid-state and in solution.

The goal of the xPc research program is to scientifically and technically evaluate the capacity of a multicellular liquid-liquid centrifuge technique to intensify both reaction conditions and extraction/purification methods. Centrifugal Partition Chromatography (CPC) is a separation technique made up of a series of interlinked cells disposed in a rotor. A first liquid phase is held stationary in the individual cells through the application of a centrifugal force. A second liquid phase can then be pumped through the cells in a continuous manner. This purification method has been principally developed in the field of natural product chemistry. Nevertheless, certain characteristics such as the absence of solid support, hydrodynamics, and a continuous function mode makes this technique well suited to the development of new applications, notably in areas where solvent use and raw material is restricted. This can also be applied to process development which is equally limited in the pharmaceutical and cosmetic industries due to the rising cost of raw materials, catalysts, and the complexity of certain products (natural oils and extracts). These constraints could be reduced by the development of new and more efficient processes. The first phase of this program is dedicated to technical research e.g. characterization and modelization. Methodology, aimed at industrial applications in the areas of enzyme catalysis and purification of natural products in the displacement mode, will then be developed. This phase, in terms of know-how, simulation and methodology, will help in the overall technical development including design optimization, scale changes, and technological and economical analyses. This project involves 3 public research groups and 2 private industries. The Chemical Engineering-Environment and Agri-food laboratory, UMR 6144, has over 15 years of experience in hydrodynamics and CPC transfer as well as in the improvement and design of CPC instruments. The Molecular Chemistry Institute of Reims (ICMR) is a research group at the forefront of methodology dedicated to the purification of natural products which use CPC in the displacement mode. The Chemical Engineering laboratory, UMR 5503, has a solid background in the area of liquid-liquid processes, extrapolation, and reactor intensification. Pierre Fabre develops, produces and commercializes medicine in many pharmaceutical areas, notably cancer research for over 30 years. The Rousselet-Robatel-Kromaton industry is a specialist in centrifugal processes and manufacturing of CPC instruments from laboratory to pilot plant scale. Bringing together these well known groups in a concerted research effort is strength of this research proposal. Our goal is not only to achieve and finalize this ambitious project, but to favor scientific exchanges between researchers with different backgrounds and scientific cultures in order to encourage innovation in an interdisciplinary manner. The presence of an end user and an instrument developer increases the technological coherence of the overall project (construction, mechanic constraints, cost, security, extrapolation) as well as the industrial coherence (insertion in process chain, separation and reaction performance). In the call for projects “Durable Chemistry and Innovation” the xPC project is in the “Efficient Process and Reaction” category. The goal of the xPC program is the modelization and development of technical applications and is thus an industrial research project.

I-CHEM’ALGAE (“Challenge 5 - Sécurité Alimentaire et Défi Démographique Ressources biologiques, exploitation durable des écosystèmes et Bioéconomie”; axe 6 - Bioéconomie: technologies spécifiques et approches système.”) aims to develop an original integrated strategy to optimize microalgae biorefinery, based on metabolomics (by using chemometric tools to merge multimodal and multiscale spectroscopic data sets) and process engineering (including cultivation in photobioreactors, deconstruction/fractionation aspects). This strategy will address the technological issues related to chemotyping/dereplication of microalgae and cell resistance to develop an optimized and intensified biorefinery approach for microalgae entire valorisation. Indeed, even if microalgae are mainly known for their potential in biofuel production, they could represent innovative and biologically promising resources for high added value sectors such as cosmetics, provided that efficient tools are available for their chemical characterization. This collaborative project, involves three academic and one industrial partners, the latter being specialized in the development and production of cosmetic ingredients. This project will thus exploit the synergy between process engineering, analytical, chemoinformatic and phyto-chemistry skills with those of a major player in the development of blue biotechnology in the cosmetic field (Givaudan) in order to meet the scientific and technological objectives while taking into account environmental and industrial concerns (solvent selection and time requirement of the global workflow). Thus the PRCE financing tool is clearly consistent with the objectives of this project. Beside a coordination task, the scientific and technical program of i-Chem’Algae is organized in 4 main tasks developed over 36 months. The innovative nature is reflected by the global project structure that aims to provide an integrated approach for microalgae biorefinery, but also within the three technical tasks. Task 1 aims to develop a chemical and micro-mechanical pattern recognition model for microalgae screening according to the global nature of their chemical composition and cell resistance, these two aspects being of primary importance for both biorefinery engineering and valorisation. The main novelty consists in the fusion of multi-modal and multi-scale non-invasive spectroscopy data stets recorded on entire cell to build the pattern recognition model. The objective of task 2 is to develop a procedure for microalgae biomass deconstruction and fractionation guided by the Task 1 results and to produce chemically simplified extracts, which will be further submitted to a fine chemical profiling (Task 3). Task 2 also includes cultivation under photobioreactor control in order to allow a continuous state biomass production. The objective of Task 3 is to develop procedure for the chemical characterization of small metabolites mainly based on dereplication, Nuclear Magnetic Resonance, chemometric tools and databasing and to connect these data with biological activities. Moreover, a combination of original tools such as LC-NMR and artificial intelligence will be implemented to speed up the de novo structure elucidation process in case of novel compounds. Finally, Task 4, aims to provide a technical and economic evaluation of the proposed integrated strategy for the development of microalgae-based new cosmetic ingredients. I-Chem'Algae is thus a research project with 3 kinds of final deliverables including knowledge acquisition by developing an original strategy for microalgae biorefinery - this integrated approach being transferable on other starting materials -, societal aspects with new concepts for the use of alternative raw materials (here microalgae) compatible with the concepts of circular economy and the use of sustainable processes and finally industrial developments by the development of original microalgae-derived cosmetic active ingredients.

Fluorine-containing organic molecules play a major role in medicinal chemistry, asymmetric synthesis, crop sciences and material sciences. The selective removal of one fluorine atom from a polyfluorinated functional group by C–F activation is a powerful tool for the synthesis of new fluorinated molecules. This proposal is based on the recent discovery of two unprecedented C–F activation processes involving lanthanide metals: (i) the transformation of trifluoromethylated benzofulvenes into difluorovinylindenes and (ii) the selective formation of 1,2,4,5-tetrafluorobenzene from the reaction of ytterbium with pentafluorobenzene. The aim is the understanding of the aforementioned reactions and the screening of their potential for future applications in organic and organometallic chemistry, with a special interest in the synthesis of biologically active compounds. The outcomes should have an important impact on the understanding and use of lanthanide metals in C–F activation processes.