Carbohydrates are ubiquitous across all aspects of molecular biology. They exist in both conjugated and unconjugated forms and are critical to a wide-range of biological events. For example, carbohydrate domains on glycoproteins govern folding and increase resistance to proteases. Glycolipids participate in immune surveillance, inflammatory responses, and cellular recognition. Unconjugated carbohydrates are similarly important, serving as prebiotics and antimicrobials in human milk where they assist in the development of the microbiome. Given their significance as therapeutic and diagnostic tools, it is important to understand carbohydrate involvement in the pathogenesis of disease. Unfortunately, the inability to obtain homogeneous oligosaccharides and glycoconjugates (fluorescently labeled or isotopically enriched) is a fundamental challenge to understanding carbohydrate function.  This project focuses on developing new strategies and tactics to synthesize homogeneous oligosaccharides, specifically human milk oligosaccharides (HMOs), for biological evaluation.

II. Neuroscience.

Our laboratory has a focus on the synthesis and evaluation of biologically relevant natural products. We have recently launched a total synthesis-based initiative directed toward the development of lead compounds of potential value in the treatment of neurodegenerative disorders, such as Alzheimer’s, Huntington’s, and Parkinson’s diseases. Neurodegenerative disorders afflict a growing segment of the population. The development of clinically useful therapeutic options for those affected has thus emerged as a pressing public health concern. However, the development of broadly useful, demonstrably effective anti-neurodegenerative agents remains an elusive goal. Our research group has identified a number of structurally interesting natural products that possess some demonstrated central nervous system (CNS) activity. Our objectives are to accomplish the total synthesis of our chosen target, hopefully in a noteworthy fashion, and to validate the reported biological activity with synthetic material. Next, using diverted total synthesis and derivatization of the synthetic natural product, we chart an SAR profile through the preparation and evaluation of structurally modified analogues. The most promising leads are  subjected to structural iterations and more exhaustive biological studies, including attempted target identification.