Synthesis of fluorinated Exo-glycals mediated by selectfluor

Fluorinated carbohydrates constitute a very important class of mechanistic probes for glycosyl processing enzymes. In the mechanistic studies of retaining glycosidases, 2-fluoro-glycosides have become key tools to evidence a transient covalent process as well as to identify the catalytic nucleophiles. Fluorinated sugars have also been successfully exploited as mechanistic probes for glycosyltransferases. Exo-glycals are anomeric enol-ethers derived from carbohydrates in which the double bond is exocyclic. This class of molecules has found many applications as synthetic intermediates. In addition, some exo-glycals have been designed as transition-state analogues of enzymatic glycosyl transfers and were shown to be extremely potent sialyltransferase inhibitors. Interestingly, exo-glycals derived from galactofuranose (Galf) displayed unique time-dependent inactivation properties against UDP-galactopyranose mutase (UGM), an essential enzyme implied in the biosynthesis of the cell wall of important pathogens. Importantly, we could show that the corresponding fluorinated exo-glycal improved the properties of these inhibitors. Beyond carbohydrate chemistry, phosphonates and their fluorinated analogues constitute a very important class of molecules that have found applications in both material and pharmaceutical sciences.