Fluorine-Directed Automated Mannoside Assembly

Automated glycan assembly (AGA) on solid support has become invaluable in reconciling the biological importance of complex carbohydrates with the persistent challenges associated with reproducible synthesis. Whilst AGA platforms have transformed the construction of many natural sugars, validation in the construction of well-defined (site-selectively modified) glycomimetics is in its infancy. Motivated by the importance of fluorination in drug discovery, the biomedical prominence of 2-fluoro sugars and the remarkable selectivities observed in fluorine-directed glycosylation, fluorine-directed automated glycan assembly (FDAGA) is disclosed. This strategy leverages the fluorine atom for stereocontrolled glycosylation on solid support, thereby eliminating the reliance on O-based directing groups. The logical design of C2-fluorinated mannose building blocks, and their application in the fully (alpha-)stereocontrolled automated assembly of linear and branched fluorinated oligomannosides, is disclosed. This operationally simple strategy can be integrated into existing AGA and post-AGA protocols to augment the scope of programmed carbohydrate synthesis.

Automated summary

Automated glycan assembly (AGA) on solid support is a valuable tool for reproducible synthesis of complex carbohydrates. In this study, the researchers introduced a fluorine-directed automated glycan assembly (FDAGA) strategy, which utilizes the fluorine atom for stereocontrolled glycosylation on solid support, enabling the synthesis of well-defined fluorinated glycomimetics.