Synthesis of fluorinated Thomsen–Friedenreich antigens: direct deoxyfluorination of αGalNAc-threonine tert-butyl esters

Abstract

Selectively 6-fluorinated analogs of the tumor-associated T_Nantigen Fmoc-Thr(α-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.