Les travaux décrits dans ce manuscrit portent sur l’étude de nanostructures obtenues par auto-assemblages d’amphiphiles diacétyléniques polymérisables. Essentiellement deux familles de composés ont été étudiées (micelles sphériques et rubans en bicouches) et valorisées, d'une part, pour des applications biomédicales et, d’autre part, pour la catalyse. Dans un premier temps, des micelles cationiques polymérisées assemblées à partir d’amphiphiles diacétyléniques sont synthétisées. Ces micelles ont été valorisées pour la prise en charge et la transfection d’ARN interférents in vitro. Ensuite, un catalyseur micellaire « biocompatible » incorporant du cuivre a été développé pour promouvoir des transformations chimiques in vitro. Nos études ont ainsi porté sur la réaction de cycloaddition 1,3-dipolaire de Huisgen que nous avons mise en œuvre dans le compartiment intracellulaire. Enfin, nous nous intéressons à la synthèse et à la formulation d’amphiphiles diacétyléniques en architectures supramoléculaires qui ont été utilisées pour la catalyse asymétrique et semi-hétérogène de la réaction d'aldolisation. / The work described in this manuscript focuses on the study of nanostructures obtained by self-assembly of polymerizable diacetylenic amphiphiles. Two families of compounds have been studied (spherical micelles and bilayer ribbons) and used for biomedical applications on the one hand and for catalysis on the other. At first, polymerized cationic micelles assembled from diacetylenic amphiphiles are synthesized. These micelles were valorized for the transfection of small interfering RNAs in vitro. Then a "biocompatible" micellar catalyst incorporating copper was developed to promote in vitro chemical transformations. Our studies focused on the Huisgen 1,3-dipolar cycloaddition that we implemented in the intracellular compartment. Finally, we are interested in the synthesis and formulation of supramolecular architectures from diacetylenic amphiphiles. These systems have been used for the asymmetric and semi-heterogeneous catalysis of the aldol reaction.

Project I. Cinchona alkaloid-derived quaternary ammonium salts have been successfully used as phase-transfer catalysts, particularly in asymmetric alkylations. Our group applied this type of catalyst in the synthesis of β-hydroxy α-amino acids via aldol reactions and discovered that the Park-Jew catalyst afforded good yields and good enantiomeric excess of the syn diasteromers, but negligible diastereoselectivity. This project was therefore focused on the synthesis of novel cinchonidine-derived catalysts with the Park-Jew catalyst as the lead structure. The C3 position of cinchonidine nucleus was modified to achieve dimers and catalysts possessing electron-deficient alkyne and alkene moieties. Synthesized catalysts were tested in the asymmetric aldol reactions, with some of them yielding improvements relative to the Park-Jew catalyst. Project II. Celogentin C is a natural product that was isolated from the seeds of Celosia argentea by Kobayashi in 2001. It is the most potent inhibitor of the polymerization of tubulin from among the celogentin family. The novel bicyclic octapeptide structure contains unusual linkages between leucine β-carbon and indole C-6 of tryptophan and between tryptophan indole C-2 and imidazole N-1 of histidine. The project culminated in the first total synthesis of celogentin C. Reaction conditions were developed by synthesizing the left-hand ring and the right-hand ring separately, and the total synthesis was accomplished via a left to right strategy. Key transformations in the construction included intermolecular Knoevenagel condensation, radical conjugate addition, macrolactamization, and oxidative coupling.