Synthesis of gem -Difluoro Spirocyclic Cyclopropyl Mannosyl-1-phosphate Analogues and Chemoenzymatic Preparation of ADP- and GDP-Spirocyclopropyl-mannose

We report here the first synthesis of a gem-difluoro spirocyclopropyl phosphonate linked at the anomeric position of a carbohydrate. Three strategies involving carbenes either at the CF₂, at the phosphonate, or on the sugar ring were investigated, but only the glycosylidene carbene produced the fluorinated cyclopropane. Among the four possible stereoisomers, phosphonates with α-cis and α-trans configurations were generated with high stereoselectivities. ADP- and GDP-spirocyclopropyl-mannoses were then generated chemically and chemoenzymatically, respectively.