The target-driven component of the Sorensen Lab concerns itself with the design and execution of concise, scalable, and creative syntheses of molecules with both biological and structural interest. While we do not limit the choice of targets to the themes below, we have found our thinking to be guided by the incorporation of cascades and C–H functionalization in synthetic designs which, through diversification, will allow for the interrogation of biological activity of targets and their analogues.
Cascades – Nature often employs multi-reaction cascade sequences to rapidly develop molecular complexity from simple starting materials. Inspired by these powerful transformations, we incorporate both biomimetic (proposed biosynthetically) and bio-inspired (designed de novo) cascades into our synthetic designs in order to expediently access targets of interest. The Diels–Alder cycloaddition has often been a lynchpin in these designs.
Relevant References
- Norris, M. D.; Perkins, M. V.; Sorensen, E. J. Org. Lett. 2015, 17, 668-671.
- Reber, K. P.; Tilley, S. D.; Carson, C. A.; Sorensen, E. J. J. Org. Chem. 2013, 78, 9584-9607.
- Zapf, C. W.; Harrison, B. A.; Drahl, C.; Sorensen, E. J. Angew. Chem. Int. Ed. 2005, 44, 6533-6537.
- Vanderwal, C. D.; Vosburg, D. A.; Weiler, S.; Sorensen, E. J. J. Am. Chem. Soc. 2003, 125, 5393-5407.
C–H Functionalization – The recent development powerful C–H functionalization reactions is increasingly allowing for the treatment of C–H bonds as functional group handles. Through our involvement in the NSF Center for Selective C-H Functionalization (NSF-CCHF), we are able to leverage the knowledge of premier methodology-, computation-, and mechanism-focused groups to intelligently apply these new reactions towards short, non-obvious syntheses.
Relevant References
- Bedell, T.A.; Hone, G.A.B.; Valette, D.; Yu, J.-Q.; Davies, H.M.L.; Sorensen, E.J. Angew. Chem. Int. Ed. 2016, 55, 8270.
- Bedell, T. A.; Hone, G. A. B.; Du Bois, J.; Sorensen, E. J. Tetrahedron Letters (Memorial Symposium-in-print for Harry Wasserman) 2015, 56, 3620-3623.
- Siler, D. A.; Mighion, J. D.; Sorensen, E. J. Angew. Chem. Int. Ed. 2014, 53, 5332-5335.
Biological Activity – Natural products are often noted for their effects on biological systems, with many drugs either being potent secondary metabolites or derived therefrom. Towards discovering new entities that can function as anti-infectives, we are interested in exploring the biological activities of natural products and synthetically produced derivatives through collaboration.
Relevant References
- Lotesta, S. D.; Liu, J.; Yates, E. V.; Krieger, I.; Sacchettini, J. C.; Freundlich, J. S.; Sorensen, E. J. Chem. Sci. 2011, 2, 1258-1261.
- Freundlich, J. S.; Lalgondar, M.; Wei, J. R.; Swanson, S.; Sorensen, E. J.; Rubin, E. J.; Sacchettini, J. C. Tuberculosis 2010, 90, 298-300.
- Buey, R. M.; Calvo, E.; Barasoain, I.; Pineda, O.; Edler, M. C.; Matesanz, R.; Cerezo, G.; Vanderwal, C. D.; Day, B. W.; Sorensen, E. J.; Lopez, J. A.; Andreu, J. M.; Hamel, E.; Diaz, J. F. Nat. Chem. Biol. 2007, 3, 117-125.
- Evans, M. J.; Saghatelian, A.; Sorensen, E. J.; Cravatt, B. F. Nature Biotech. 2005, 23, 1303-1307.
- Vanderwal, C. D.; Sorensen, E. J.; Cravatt, B. F. Angew. Chem. Int. Ed. 2003, 42, 5480-5484.