The Frederich Laboratory
Complex Molecule Synthesis & Molecular Pharmacology
Program Overview
Research in the Frederich Lab focuses on the structure, function, and chemical synthesis of bioactive molecular architectures with latent translational potential. We draw our inspiration from complex natural products and orphaned synthetic drugs that might be reprogrammed to modulate difficult biological targets. Our goal is not only to build target structures but to exploit them as a starting point for the design of new functional molecules. This approach necessarily shifts the emphasis from pure target-oriented thinking toward capturing the chemical space around bioactive scaffolds. In short, we view complex molecule synthesis as a gateway to enhance opportunities for synthesis–biology iteration and to (re)program molecular function more broadly. We are currently interested three fundamental questions:
(1) Can we improve access to natural product chemical space?
(2) Can the pharmacology of electrophilic natural products be reprogrammed?
(3) Can we reengineer small molecules to target protein-protein interactions more effectively?
Co-workers under my supervision are trained as molecular architects, synthetic innovators, and entrepreneurs. My group is organized into two overlapping research arms. A fundamental research arm aims to develop enabling synthetic strategies and tactics that (i) expand entry to natural product chemical space and (ii) expedite the design of non-natural compositions of matter with enhanced pharmacological profiles. This research fuels a complementary translational research arm that focuses on multidisciplinary efforts to elucidate the functional profiles of our targets and harness their potential.
Bioactive Natural Products
Natural products (NPs) are central to research in my group. These biogenic small molecules occupy remote areas of chemical space beyond the reach of conventional synthetic drugs. They also come refined by evolution to cross cell membranes and interface with biomolecules. However, despite these features, NPs rarely emerge as approved drugs. Instead, NP analogs and NP-inspired structures have enjoyed the most success. This points to an emergent question in the field: How can we more effectively navigate NP chemical space to arrive at therapeutic leads? We believe that synthetic chemistry holds the key to harnessing the full potential of NP-based drug discovery.
Targets of interest to us demand innovative chemical solutions and harbor significant translational potential. These features are exemplified by the molecules below:
Strategic Partnerships
Scientists in my group learn to collaborate. We are interested in the synergistic relationship between fundamental chemistry innovation and translational research. Thus, extending our discoveries into the real world is an important objective. This is often approached in partnership with early-stage companies. Ongoing academia-industry partnerships include:
