Nouvelles approches pour la synthèse de S- et N-glycosides ainsi que de C-furanosides

Glycosides represent important carbohydrate motifs found in numerous natural products, as well as potential bioactive drugs and chemicals. Compared to O-glycosides, S- and C-glycosides are more stable under acidic conditions or in the presence of enzymes. N-glycosides also occupy a special position as they are present in DNA/RNA in the form of nucleosides. As a result, the efficient synthesis of various S-, N- and C-glycosides has attracted considerable attention. During my PhD, my research focused on developing new approaches for the synthesis of S-, N- and C-glycosides throught C-H actication strategy and metal-free catalytic functionalization of sugars.We first introduced the synthesis of S-glycosides via the functionalization of thiosugars. Over the past decades, C-S bond formation has been extensively studied through cross-coupling reactions catalyzed by transition metals, photocatalysis and electrocatalysis. In contrast, C-H activation strategies remain underexplored, with only one example. Our first project foucused on the synthesis of 1-thiotrehaloses and 1-thiolated glycals via Cu-catalyzed C-H thiolation at the pseudo-anomeric position of glycals bearing an 8-amidoquinoline directing group, using thiosugars and thiols as coupling partners. In addition, we also developed a metal-free catalytic functionalization of thiosugars for the construction of alkenylthioglycosides, which provides an attractive alternative to metal-based methods.Subsequently, we turned our attention to the synthesis of N-glycosides. The construction of glycosidic bonds in N-glycosides has relied on polar reactions between N-nucleophilies and glycosyl oxocarbenium intermediates, radical N-glycosylation involving glycosyl radicals and N- nucleophiles, and Ferrier-type glycosylation of glycals. My projects-C-H amination of sialic glycals and Ferrier-type reaction of glycals without the use of external activator-expand the methodological toolbox for the efficient synthesis of N-glycosides.Finally, we focused on the synthesis of C-furanosides, given the extensive methods already developed for the construction of C-pyranosides. We developed a new approach for the synthesis of C3-aryl furanosides through Pd-catalyzed C(sp3)-H activation, enabled by a DMAQ directing group. In contrast to existing methods that functionalize the anomeric position of sugars, this strategy introduces (hetero)aryl groups at the C2 position of the furanose ring, thereby expanding the scope of C-glycoside synthesis. Moreover, this approach exhibits high 2,3-cis stereoselectivity and is compatible with a wide range of readily available aryl iodides. Conditions for the removal of the DMAQ directing group and selective deprotection of the OBn protecting groups were also presented. DFT calculations provide evidences of observed cis stereoselectivity of the reaction.