The development of synthetic organic chemistry that provides access to complex bioactive molecules and their analogs is central to our research effort. These studies provide material to explore the biological properties of these molecules. Many of these molecules are natural products, which have long been the primary source of the majority of therapeutic agents and candidate molecules. Molecules under investigation include potential antitumor agents (like maoecrystal V and pellynol I), immunosuppressive agents ( like dalesconol A) and molecules that modulate pain response (like grandisine A). Additionally, a program focused on the development of new phosphatase inhibitors is also underway. The chemical synthesis of these molecules is performed in our laboratories, while the testing of their biological properties is performed in collaboration with the Doyle lab at Syracuse (antitumor properties) and the Kerr lab at SUNY Upstate Medical Center (phosphatase inhibition assays and immunology).
A second long-term research objective is the development of new methods for carbon-carbon bond formation. Catalytic techniques are of special interest because catalysts for organic reactions are not limited to simple rate acceleration, but can be modified to control the relative and absolute stereochemistry of the reaction products. Recently we have demonstrated that alkynes are useful nucleophiles in metal catalyzed addition reactions to cyclopropenes (using palladium catalysis) and activated ketones and aldehydes (using rhodium catalysis). These reactions occur under mild conditions that are tolerant of functional groups (alcohols, ketones, carboxylic acids, etc.) that have to be protected under standard conditions. Current efforts are focused on the development of modified methods that will control the enantioselectivity of these transformations.
Dhondi, P. K.; Carberry, P.; Choi, L. B.; Chisholm, J. D. Addition of Alkynes to Aldehydes and Activated Ketones Catalyzed by Rhodium-Phosphine Complexes. J. Org. Chem. 2007, 72, 9590-9596.
Yin, J.; Gallis, C. E.; Chisholm, J. D. Tandem Oxidation/Halogenation of Aryl Allylic Alcohols Under Moffatt-Swern Conditions. J. Org. Chem. 2007, 72, 7054-7057.
Dhondi, P. K.; Carberry, P.; Chisholm, J. D. Ligand Effects in the Rhodium-Catalyzed Addition of Alkynes to Aldehydes and Diketones. Modification of the β-Diketonate Ligand. Tetrahedron Lett. 2007, 48, 8743-8746.
Ganci, G. R.; Chisholm, J. D. Rhodium-Catalyzed Addition of Aryl Boronic Acids to 1,2-Diketones and 1,2-Ketoesters. Tetrahedron Lett. 2007, 48, 8266-8269.
Yin, J.; Chisholm, J. D. Palladium-Catalyzed Addition of Alkynes to Cyclopropenes. Chem. Commun. 2006, 6, 632-634.