A mild and convenient method for the synthesis of reverse glycosyl fluorides (RGFs) has been developed that is based on the silver‐promoted radical dehydroxymethylative fluorination of carbohydrates. A salient feature of the reaction is that furanoid and pyranoid carbohydrates furnish structurally diverse RGFs bearing a wide variety of functional groups in good to excellent yields. Intramolecular hydrogen atom transfer experiments revealed that the reaction involves an underexploited radical fluorination that proceeds via β‐fragmentation of sugar‐derived primary alkoxyl radicals. Structurally divergent RGFs were obtained by catalytic C−F bond activation, and our method thus offers a concise and efficient strategy for the synthesis of reverse glycosides by late‐stage diversification of RGFs. The potential of this method is showcased by the preparation and diversification of sotagliflozin, leading to the discovery of a promising SGLT2 inhibitor candidate.

Campylobacter jejuni is the leading cause of human diarrheal diseases and has been designated as one of highly resistant pathogens by the World Health Organization. The C. jejuni capsular polysaccharides feature broad existence of uncommon 6dHepp residues and have proven to be potential antigens to develop innovative antibacterial glycoconjugation vaccines. To address the lack of synthetic methods for rare 6dHepp architectures of importance, we herein describe a novel and efficient approach for the preparation of uncommon D-/L-6dHepp fluorides that have power as glycosylating agents. The synthesis is achieved by a C1-to-C5 switch strategy relying on radical decarboxylative fluorination of uronic acids arising from readily available allyl D-C-glycosides. To further showcase the application of this protocol, a structurally unique hexasaccharide composed of →3)-β-D-6didoHepp-(1→4)-β-D-GlcpNAc-(1→ units, corresponding to the capsular polysaccharide of C. jejuni strain CG8486 has been assembled for the first time. The assembly is characterized by highly efficient construction of the synthetically challenging β-(1,2-cis)-D-ido-heptopyranoside by inversion of the C2 configuration of β-(1,2-trans)-D-gulo-heptopyranoside, which is conveniently obtained by anchimerically assisted stereoselective glycosylation of the orthogonally protected 6dgulHepp fluoride. Ready accessibility of 6dHepp fluorides and the resulting glycans could serve as a rational starting point for the further development of synthetic vaccines fighting Campylobacter infection.

No abstract

No abstract