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.