Synthesis of fluorinated Thomsen-Friedenreich antigens: direct deoxyfluorination of alpha GalNAc-threonine tert-butyl esters

Selectively 6-fluorinated analogs of the tumor-associated T-N antigen Fmoc-Thr(alpha-O-GalNAc)-OtBu can be efficiently prepared using DAST-mediated de(hydr) oxyfluorination reactions of preformed and orthogonally protected glycosyl amino esters without affecting the labile protecting groups and O-glycosidic linkages. The resulting mono-and difluorinated T-N analogs are interesting building blocks for non-hydrolyzable mucin-type antigen mimetics, as illustrated by the unprecedented synthesis of two different multiply fluorinated Thomsen-Friedenreich derivatives. The reported deoxyfluoro antigen analogs represent important functional probes for carbohydrate-binding proteins and glycosyl-processing enzymes.