Dr. Indrajeet Sharma of the University of Oklahoma will develop new sustainable methods for synthesizing carbohydrate-based molecules that are important in medicines, vaccines, and biological systems. Many useful carbohydrate structures remain difficult to prepare using current chemical methods because they often require harsh acids, expensive precious metals, and multiple reaction steps that generate chemical waste. This project will introduce cleaner and more efficient strategies that use sulfur chemistry, visible light, and earth-abundant metals, such as iron and copper, to construct complex sugar molecules under mild conditions. The research would support innovation in biotechnology by developing advances that could improve the ability to produce carbohydrate-inspired compounds needed for drug discovery, vaccine development, biomaterials, and healthcare applications. The project will also train postdoctoral fellows, graduate students, and undergraduate students in modern synthetic chemistry, catalysis, photochemistry, and computational chemistry. Outreach activities, including Science Café programs, community engagement events, and educational courses, will help increase public understanding of chemistry and inspire future scientists and engineers.
Technically, this project will develop sulfur-mediated strategies for stereo-controlled glycosylation, with emphasis on synthesizing challenging 1,2-cis furanosidic linkages and structurally modified sugars. The research will investigate how sulfur can synergize with reactive carbene and nitrene intermediates generated through visible-light photochemistry or iron- and copper-based catalysis to activate thioglycosides and 4-thiofuranoses under mild conditions. These strategies will enable glycosylation with O-, N-, C-, and S-nucleophiles while avoiding harsh acids and precious-metal catalysts. The project will also develop direct C–H activation methods to prepare stable thio- and seleno-sugars without requiring preinstalled leaving groups, as well as skeletal-editing approaches to transform natural oxysugars into thio-, imino-, and carbo-sugars. Mechanistic and computational studies will provide fundamental insight into the conformational and electronic factors controlling stereoselectivity. Together, these studies will establish practical and sustainable methods for preparing diverse glycoconjugates and glycomimetics relevant to chemical biology, medicinal chemistry, and advanced biotechnology.
This award reflects NSF’s statutory mission and has been deemed worthy of support through evaluation using the Foundation’s intellectual merit and broader impacts review criteria.