Most of the natural products produced by microorganisms or plants are not meant to bind to human proteins. However, for many years, microorganisms and plants have evolved to produce small ligands (or natural products) for their macromolecular targets within living organisms, and many human protein targets contain structural domains similar to the targets with which small ligands (or natural products) have coevolved. Through the natural selection process, natural products possess a unique and vast chemical diversity and have been evolved for optimal interactions with biological macromolecules. Therefore, natural products have proven to be by far the richest source of novel compound classes for biological studies and an essential source of new drug discovery.

 Research in the Hong group focuses on using chemical tools, in particular small molecules, to understand the signaling pathways in biology. Herein, we detail our efforts for the synthesis and biological characterization of natural products, including largazole (a histone deacetylase inhibitor), subglutinols (immunosuppressive natural products), and manassantins (HIF-1 downregulators).