This talk will describe the development of a fluorination/glycosylation strategy for the synthesis of 2`-fluorinated nucleosides. Electrophilic fluorination of a glycal intermediate with N-fluorobenzenesulfonimide (NFSI) proceeds in a highly diastereoselective fashion to produce the respective 1`,2`-difunctionalized furanoside species. Mechanistic studies demonstrated that this intermediate undergoes rapid anomeric interconversion to the thermodynamically-preferred a-sulfonimide. A scalable process was developed for isolating this TBS-protected 2`-deoxyfluorosulfonimide sugar as a crystalline, bench-stable single diastereomer. A subsequent glycosylation reaction was developed with this intermediate, and a variety of N-heterocycles were found to couple in a diastereoselective fashion. This fluorination/glycosylation strategy was also applied to the commercial route development of a potent agonist of the stimulator of interferon genes (STING) signaling pathway through the synthesis of 2`-fluoroadenosine.

Diastereoselective method for the construction of syn-2`-deoxy-2`-fluoronucleosides

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.