The Crotylation Way to Glycomimetics

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With this award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor David Mootoo of Hunter College of The City University of New York, on the synthesis and applications of carbohydrate and carbohydrate-like molecules (termed glycomimetics). Carbohydrates are involved in many biological functions including: tissue development, intracellular signaling, immune responses, cell-cell communication, cancer, metabolic disorders and pathogen infection. Understanding how carbohydrates are made and how they react adds to fundamental knowledge in cellular and molecular biology and provides insight across a variety of fields. In this context, there is a growing demand to make specific and diverse glycomimetics and to study their reactivities. While gycomimetics are desirable synthetic products, their structures are difficult to make because of their complexity. To this end, this research is developing robust methods for the synthesis of glycomimetics. This program links real-life problems in biology to chemistry solutions, thereby drawing students to the physical sciences and providing broad-based training for STEM careers. Professor Mootoo leverages potential applications to human health, the diverse 20,000-student body of Hunter College, and the unique cultural environment in New York City, to attract underrepresented high school and undergraduate students to STEM fields and the scientific workforce. The synthetic chemistry under investigation centers on the reactions of carbohydrate-derived crotylating agents with aldehydes and imines. While crotylating reagents are widely used in organic synthesis, carbohydrate variants have not been as extensively explored because of the high intrinsic reactivity of crotylating agents and the complexity and nuanced chemistry of carbohydrates. These issues are being mitigated by recent advances in organic synthesis and the expertise of Professor Mootoo in carbohydrate chemistry. A toolbox of tin, boron and silicon based reagents is being assembled and used to synthesize mimetics of biologically active glycosphingolipids and complex oligo-mannosides. The broader scientific impacts of this research include a better understanding of the immunological properties and anti-viral activities of these materials, including their role in communicable diseases. Given the often idiosyncratic reactivity of carbohydrates, this project is also unveiling unique reactivity profiles that can inform innovative paradigms for complex molecule synthesis. Finally, the research also provides excellent training for the graduate students and undergraduates that will work on this project alongside Professor Mootoo.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.