Institute of Chemistry, Academia Sinica Startup Grant (2026-2027)
Snapshots of the Reactive Sugar Intermediates: From Enzymes to Chemistry

Carbohydrate synthesis remains a formidable challenge due to the unpredictable behavior of glycosylium ion intermediates, which often leads to unreliable stereochemical outcomes. This project addresses the long-standing "1,2-cis linkage" problem by employing an enzyme-inspired (biomimetic) strategy. By using phosphate sugar analogues activated by metal catalysts, we replicate the key interactions found within enzyme active sites. This approach allows us to stabilize and study reactive intermediates in a simplified, biologically relevant environment. Our goal is to map these structural parameters to provide a predictive, step-by-step framework for glycosidic bond formation. Establishing this bottom-up strategy will not only advance fundamental glycobiology but also streamline the development of glycan-based vaccines and targeted enzyme inhibitors.