Assistant Professor,
Division of Medicinal Chemistry & Pharmacognosy
Riffe Building Room 634
496 W. 12th Ave.
Columbus, OH 43210
E-Mail: fuchs@pharmacy.ohio-state.edu
Phone: (614) 247-7377, Fax: (614) 292-2435
Applications of synthetic chemistry in drug discovery
Natural products have always played a key role for medicinal chemists in the process of drug discovery. Employing the structural scaffolds and biological activity of these compounds as a starting point, our group intends to use synthetic chemistry as a tool to probe biological problems. Specifically, we will utilize synthetic methods to prepare these bioactive natural products and their analogues, gain insight into the structure–activity relationships of ligand/receptor systems, and investigate biosynthetic pathways. The unique molecular architectures of natural products also encourage the improvement of existing synthetic methodology and the development of new methods in order to solve challenging structural issues. Synthetically, we will lean heavily on cycloaddition and rearrangement reactions to quickly generate molecular complexity and ultimately lead to the construction of desired target molecules. Variations in our synthetic strategies will also provide access to a wide array of rationally designed, analogous structures. Our work will then rely on computational chemistry and biology to unravel the critical roles that functional groups and stereochemistry play in the activity of these compounds. Ultimately, the goal is not simply to prepare these natural products, but to improve upon their activity and pharmacological profiles.
Major areas of emphasis are in the preparation of novel antibiotics and anticancer agents with unique or interesting mechanisms of action through selective inhibition of a specific protein or enzyme target. Representative natural products currently of interest in the group are platensimycin, a selective inhibitor of bacterial type II fatty acid biosynthesis; abyssomicin, an inhibitor of p-aminobenzoate (PABA) biosynthesis; and sespendole, an inhibitor of lipid droplet synthesis in macrophages. Methods which will be investigated during the course of these projects include enantioselective [4+3]-cycloaddition reactions, asymmetric inverse electron demand Diels–Alder cycloaddition reactions, and “biomimetic” cyclization reactions.
Intramolecular Diels–Alder/1,3-Dipolar Cycloaddition Cascade of 1,3,4-Oxadiazoles. Elliott, G. I.; Fuchs, J. R.; Blagg, B. S. J.; Ishikawa, H.; Tao, H.; Yuan, Z.-Q.; Boger, D. L. J. Am. Chem. Soc. 2006, 128, 10589–10595.
Indol-2-one Intermediates: Mechanistic Evidence and Synthetic Utility. Total Syntheses of (±)-Flustramines A and C. Fuchs, J. R.; Funk, R. L. Org. Lett. 2005, 7, 677–680.
Total Synthesis of (±)-Perophoramidine. Fuchs, J. R.; Funk, R. L. J. Am. Chem. Soc. 2004, 126, 5068–5069.
Total Synthesis of (±)-Lennoxamine and (±)-Aphanorphine by Intramolecular Electrophilic Aromatic Substitution Reactions of 2-Amidoacroleins. Fuchs, J. R.; Funk, R. L. Org. Lett. 2001, 3, 3923–3925.
Intramolecular Electrophilic Aromatic Substitution Reactions of 2-Amidoacroleins: A New Method for the Preparation of Tetrahydroisoquinolines, Tetrahydro-3-benzazepines, and Hexahydro-3-benzazocines. Fuchs, J. R.; Funk, R. L. Org. Lett. 2001, 3, 3349–3351.
Reactions of SmI2 with Alkyl Halides and Ketones: Inner Sphere vs Outer Sphere Electron Transfer in Reactions of Sm(II) Reductants. Miller, R. S.; Sealy, J. M.; Shabangi, M.; Kuhlman, M. L.; Fuchs, J. R.; Flowers, R. A. J. Am. Chem. Soc. 2000, 122, 7718–7722.
The Effect of Cosolvent on the Reducing Power of SmI2 in Tetrahydrofuran. Shabangi, M.; Sealy, J. M.; Fuchs, J. R.; Flowers, R. A. Tetrahedron Lett. 1998, 39, 4429–4432.
The Effect of Lithium Bromide and Lithium Chloride on the Reactivity of SmI2 in THF. Fuchs, J. R.; Mitchell, M. L.; Shabangi, M.; Flowers, R. A. Tetrahedron Lett. 1997, 38, 8157–8158.
July 2007–Present. Assistant Professor, Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH.
February 2005–June 2007. Research Associate in Synthetic Organic/Medicinal Chemistry, The Scripps Research Institute, La Jolla, CA.
June 1998–January 2005. Ph.D. Candidate in Synthetic Organic Chemistry, The Pennsylvania State University, University Park, PA.
