Three-component radical strategy to aryl C-glycoside bioisosteres

Aryl C-glycosides are an important class of molecules comprising natural products and biologically active compounds which have found wide application as drugs in the treatment of type 2 diabetes. On the other hand, the study of three-dimensional analogues of aryl C-glycosides is still largely underexplored. This thesis project aims at developing a synthetic method to efficiently access bicyclopentyl (BCP) C-glycosides. These newly designed compounds feature a BCP moiety that effectively mimics a p-disubstituted aryl ring intended to provide the molecules with enhanced drug-like properties, such as increased lipophilicity and higher water solubility. Our synthetic protocol involves a three-component radical reaction that occurs under thermal conditions. The optimized process is remarkable for its operational simplicity and could be applied to the functionalization of several carbohydrates including hexoses, pentoses, and disaccharides. The mechanism of the reaction was also investigated, which allowed to confirm the radical nature of the transformation.