With this CAREER award, the Chemical Synthesis Program of the NSF Chemistry Division supports the research of Professor Maciej Walczak in the Department of Chemistry at the University of Colorado in Boulder. Professor Walczak and his students develop new methods to make carbohydrates. Carbohydrates, the most abundant biopolymers, are involved in energy storage in the body. They also control molecular recognition events in the body. This research develops versatile methods for the synthesis of bioactive glycosides and glycopeptides. This research enables comprehensive studies on the function of carbohydrates in biology, and facilitates the preparation of high-value biological compounds and pharmaceutical agents. The synthetic approaches specifically enable the preparation of anti-diabetic drugs and anti-tumor antibiotics. Professor Walczak's group is well positioned to educate and train students from groups that are underrepresented in science. Outreach activities focus on improving science awareness in the local communities, specifically through education at the high school level and public presentations. The education program integrates efforts at the department and university levels to create a collaborative community of researchers working at the interface of chemistry and biology.
This research develops versatile new methodologies for the synthesis of bioactive saccharides, primarily glycosides and glycopeptides. A majority of known methods to synthesize saccharides focus on substrates in which the anomeric position is substituted with an electronegative element. This approach bears several limitations such as substrate dependence, the need for protective group manipulations, and incompatibility with free alcohol groups. The central hypothesis of this NSF CAREER award is that configurationally stable anomeric nucleophiles are engaged in stereospecific (stereoretentive) reactions under transition metal-catalyzed conditions, forming carbon-carbon and carbon-nitrogen bonds with high selectivities. These moieties are independent from the nature of the substrates and catalysts. Capitalizing on these new conceptual foundations, three specific aims are pursued: (a) the development of cross-coupling reactions of anomeric boronic acids, (b) the implementation of new chemical methods for the synthesis of carbon-glycosides, and (c) the development of new methods in the synthesis of nitrogen-linked glycoproteins. Successful realization of these aims yields novel umpolung methods that eliminate the critical problems inherent to the previous approaches. The synthetic approaches also enable the preparation of anti-diabetic drugs, anti-tumor antibiotics, glycoproteins, and glycopeptides under standardized and user-friendly conditions. The research program is also intimately connected with ongoing educational and outreach activities. An undergraduate course featuring blended learning supplemented by randomized trial to improve undergraduate pedagogy is being developed and implemented. The outreach activities focus on mentoring high-school students.
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.