Total synthesis of cyanolide A and confirmation of its absolute configuration.

Research in the Hong group focuses on using chemical tools, in particular small molecules, to understand the signaling pathways in biology. We synthesize biologically interesting natural products and screen small molecule libraries to identify modulators of biological processes. Then, we explore their modes of action in order to investigate intracellular signaling pathways and identify novel targets for drug design. In addition, we design and develop unique and efficient synthetic strategies that will allow rapid access to molecular complexity and structural diversity. Through multidisciplinary approaches, including organic synthesis, molecular biology, and cell biology, the cellular components and molecular events that embody cancer, immune response, and GPCR signaling have systematically been explored. Compounds employed in these studies could also advance the development of novel therapeutics for the treatment of human diseases.

1. Synthesis of Natural Products and Study of Mode of Action: We synthesize biologically interesting natural products and explore the modes of action in order to investigate intracellular signaling pathways and identify novel targets for drug design. Completed target molecules include largazole (a marine natural product with HDAC inhibitory activity), brasilibactin A (a cytotoxic siderophore), manassantins A and B (natural products with anti-HIF-1 activity), and subglutinols A and B (natural products with immunosuppressive activity).
2. Development of Novel Synthetic Methodology: We design and develop unique and efficient synthetic strategies which will allow rapid access to molecular complexity and structural diversity. A specific area of interest includes the development of novel methods for the stereoselective synthesis of substituted tetrahydrofurans and tetrahydropyrans.
3. Screen of Small Molecule Libraries for Identification of Small Molecule Modulators of Biological Processes: With the advent of combinatorial chemistry and other synthetic technologies, it is feasible to prepare large collections of synthetic organic molecules. These libraries are useful in providing molecules that can be used to probe relevant biological pathways. We are interested in identification of modulators of biological processes, including drug abuse and neurodegenerative diseases.

Through multidisciplinary approaches, the cellular components and molecular events that embody cancer, immune response, and neurodegenerative diseases are systematically explored. Compounds employed in these studies could also advance the development of novel therapeutics for the treatment of human diseases.