Development of New Strategies for the Synthesis of Bacterial Carbohydrates

University Of Wisconsin-Madison, Madison WI

Investigators

Abstract

With this award, the Chemical Synthesis Program of the Division of Chemistry is supporting Professor Weiping Tang of the Pharmaceutical Sciences Division of the University of Wisconsin-Madison to develop a systematic way to make bacterial carbohydrates from common precursors. Carbohydrates play important roles in inflammation, infection, cancer metastasis, and many other fundamentally important biological processes. The development of efficient methods to synthesize bacterial carbohydrates from simple, common starting materials is of value for the study of biological processes that involve these compounds. Unfortunately, bacteria use several hundred building blocks for carbohydrate synthesis that are not readily available; this is in contrast to humans and other mammals that use fewer than a dozen such building blocks. Bacterial carbohydrates need to be individually synthesized and then linked into oligomers, which is a time-consuming and technically challenging process. Professor Tang and his research team are developing synthetic strategies to address this roadblock and streamline the process for making these important compounds. These studies are also providing scientific training to graduate students and postdoctoral researchers, as well as younger generations of students traditionally underrepresented in STEM disciplines. Professor Tang actively participates in several collaborations where undergraduate and high school students partake in academic research and develop a lifelong appreciation for science. The Tang Research group is developing de novo synthesis strategies to systematically prepare a variety of bacterial carbohydrates with a high degree of stereocontrol over the glycosidic bond. In one focus area, a transition metal-catalyzed C-H amination approach is being optimized for the synthesis aminosugars and their derivatives. Simultaneously, this investigation is also providing insight in how to use C-H amination reactions in complex settings. In a second focus area, stereoselective reduction of enones followed by olefin functionalization is providing a route to rare deoxy sugars. These studies are simultaneously advancing glycoscience and synthetic organic chemistry while facilitating the study of important biological processes in bacteria. The program is also impacting chemical education at multiple levels: graduate students area gaining synthetic expertise and participating in mentoring activities that prepare them for leading positions in industry and academia, and underrepresented undergraduate and high school students and gaining hands-on experience and exposure to cutting-edge research. 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.