In our ongoing quest to facilitate the rapid synthesis of bioactive molecules, we aim to develop new reactions and easy-to-use reagents centered around the deliberate use of radicals and other reactive intermediates for C–C, C–N, and C–S bond formation. Each method is designed to enable the construction of small building blocks, the modification of natural products, and the late-stage functionalization of complex molecules. Toward our goal of exploring underutilized chemical space, we will focus our attention on designing reagents which allow for the simple installation of a variety of bioisosteres.
For some anti-cancer natural products, total synthesis remains the best strategy for obtaining sufficient amounts of compounds for a thorough biological evaluation, let alone the prospect of clinical trials. After carefully selecting our targets, our lab will focus on developing routes which are short, scalable, and designed to deliver multigram quantities of material for biological study, as well as the ability to synthesize libraries of analogs.
Moffitt’s highly collaborative environment allows us to regularly engage with numerous biologists, chemists, and clinicians in both the Department of Drug Discovery and the Chemical Biology and Molecular Medicine Program. Here we will incorporate our new methodologies in fragment-based drug discovery, the design of chemical probes, and the chemoselective modification or tagging of bioactive molecules. The newly developed reagents and methods for installation of bioisosteres will be available for collaborators and their own lead compounds.
We thank the following agencies for funding: