Oxidative Flow electrosynthesis of bioactive spiroepoxy-dienones – E-FLOX

The main goal of our collaborative project E-FLOX, between INNOVERDA, a French start-up, and the Molecular Electrochemistry Laboratory of the University of Paris, is to develop a novel and sustainable synthetic access to bioactive spiroepoxide derivatives via oxidative flow electrosynthesis. The goal is to replace the current synthetic methods suffering from problems such as low yields and use of toxic or explosive reagents. Spiro-epoxides are essential reaction intermediates used in the composition of very high added value drugs. The use of flow electrosynthesis, and more particularly electro-oxidation, should make it possible to obtain the target molecules by avoiding the use of dangerous and/or toxic reagents currently in use, an important current trend towards Green Chemistry. The goal of this project is to strongly increase synthesis yields while using environmentally friendly methods. First of all, a fundamental study based on the electrochemical oxidation of benzyl hydroxy alcohols will allow us to identify the reaction conditions compatible with the reactivity of the targeted product. In parallel, the synthesis and characterization of all the molecules potentially formed during the electrosynthesis process will be carried out in order to help us to better apprehend the mechanism. A continuous back and forth between these two parts (WP1 and WP2) shall allow us to elaborate a plan of experiment (DoE) in order to identify and optimize the key parameters of the process, initially at the laboratory scale. First encouraging results have been obtained already in the context of a collaborative pre-project between the partners allowing to develop analytical methods for the detection of the target molecule in a mixture of potential by-products, and to study its stability and reactivity. In the third part of the project (WP3), the new process will be designed as a flow electrosynthesis with the possibility of upscaling up to kg conversion, thus preparing the industrialization of the new patentable process. In this project, our approach aims to combine low-cost, low-waste and eco-responsible synthesis processes with a strong economic potential related to public health. The technology transfer is planned to be performed by licensing out of a patent to pharmaceutical companies and support for the transfer of the flow process to manufacturing plants.