Research in our laboratory is directed toward the design and synthesis of both natural products and molecules of design (unnatural products) with important structural and/or biological properties. For over two decades, my laboratory focused on the development of new methodology in organic synthesis and the application of this methodology to the synthesis of naturally occurring compounds with important biological activity. During this period, we developed the intramolecular dioxenone and intramolecular vinylogous amide photocycloadditions (J. Winkler, C. Mazur, and F. Liotta, "[2+2]Photocycloaddition-Fragmentation Strategies for the Synthesis of Natural and Unnatural Products,” Chem. Rev. 1995, 95, 2003-2020) and used these reactions to achieve the first total syntheses of the natural products manzamine A (J. Winkler, J. Axten, "The First Total Syntheses of Ircinol A, Ircinal A, and Manzamines A and D," J. Am. Chem. Soc. 1998, 120, 6425-6426), saudin (J. Winkler, E. Doherty, "The First Total Synthesis of (+)-Saudin"") and ingenol (“The first total synthesis of (+/-)-ingenol,” J. Am. Chem. Soc. 2002, 124, 9726-9728).
Recent work in the Winkler Laboratory involves both the synthesis of natural and unnatural products, i.e., molecules of Nature and molecules of design that are intended to have particular biological and/or structural properties, as well as collaborative efforts with biomedical scientists at the University of Pennsylvania School of Medicine (SOM), the Childrens’ Hospital of Philadelphia (CHOP) and the Wistar Institute to develop novel chemical substances with drug-like properties.