Christopher Dockendorff, Ph.D.
Assistant Professor, Organic and Medicinal Chemistry
Chris received his B.Sc. (co-op) in 2000 from the University of Waterloo (Ontario, Canada). While at Waterloo, Chris developed a keen interest in organic and biological chemistry during several internships in the pharmaceutical industry. This inspired him to undertake graduate studies with Prof. Mark Lautens (University of Toronto, 2000-2006), where he developed several valuable new ring-opening and ring-forming reactions and used them to prepare scaffolds for drug discovery efforts with an industrial collaborator. Chris was a post-doctoral fellow with Prof. Stephen Martin at the University of Texas at Austin (2006-2009), where he first developed an interest in diversity-oriented synthesis (DOS) and the preparation of “natural product-like” molecules. In 2009, Chris joined a new group at the Broad Institute (Cambridge, MA) under the direction of Prof. Stuart Schreiber, with a focus on medicinal chemistry and the development of chemical probes for the interrogation of important biological processes. Chris joined the Department of Chemistry at Marquette in the fall of 2012.
Our mission is to make innovative contributions to synthetic chemistry and biology by:
- Developing new or improved synthetic methods that give access to molecules with the potential to modulate important biological processes (synthetic chemistry).
- Applying these methods to the preparation of new or improved chemical probes that can be used with our collaborators to study these processes (chemical biology).
- Improving our most promising probes in an iterative process to yield compounds with the potential to impact human health (medicinal chemistry/drug discovery).
We focus on using natural products as inspiration for the design and preparation of unique molecules that are typically more accessible than the natural lead compound, but also possess improved properties, particularly for human therapeutic applications. A number of the world’s top total synthesis labs have explored such a strategy to some extent, but in general this approach is underutilized. Several examples of important drugs are provided in the figure below which highlight typical differences between traditional synthetic molecules and natural products. We endeavor to prepare molecules of intermediate complexity that can maximize the advantages of natural products while minimizing their disadvantages, as well as the disadvantages of easy-to-prepare “flat” synthetic molecules that may be more promiscuous binders and may give undesired “off-target” effects in biological systems, complicating their use as probes and drugs.
Current projects under execution or in advanced planning stages include:
- A new class of organocatalysts and potential application to the asymmetric synthesis of antibiotic and anticancer drugs.
- Novel pyridine dearomatization reactions and the synthesis of improved GPCR (G-protein coupled receptor) ligands.
- The study of “functionally-selective” GPCR signaling; the development of chemical probes to study PAR1 (protease-activated receptor 1) signaling, in collaboration with Dr. Robert Flaumenhaft (Harvard Medical School/Beth Israel Deaconess Medical Center); medicinal chemistry of PAR1 ligands with a better safety profile for use as antithrombotic agents to prevent heart attacks and stroke.
- The preparation of potent antifungal agents inspired by a natural product with a unique mode of action.
Prospective graduate students, post-doctoral fellows, and Marquette undergraduates are invited to email me to inquire about available research opportunities in my lab.
- Macrocyclic Hedgehog Pathway Inhibitors: Optimization of Cellular Activity and Mode of Action Studies. Chris Dockendorff, Marek M. Nagiec, Michel We?wer, Sara Buhrlage, Amal Ting, Partha Nag, Andrew Germain, Han-Je Kim, Willmen Youngsaye, Christina Scherer, Melissa Bennion, Linlong Xue, Benjamin Z. Stanton, Timothy A. Lewis, Lawrence MacPherson, Michelle Palmer, Michael A. Foley, José R. Perez, and Stuart L. Schreiber. Submitted.
- Discovery of 1,3-Diaminobenzenes as Selective Inhibitors of Platelet Activation at the PAR1 Receptor. Chris Dockendorff, Omozuanvbo Aisiku, Lynn VerPlank, James R. Dilks, Daniel A. Smith, Susanna F. Gunnink, Louisa Dowal, Joseph Negri, Michelle Palmer, Lawrence MacPherson, Stuart L. Schreiber, and Robert Flaumenhaft. ACS Med. Chem. Lett. 2012, 3, 232. http://dx.doi.org/10.1021/ml2002696
- Synthesis of Diverse Heterocyclic Scaffolds via Tandem Additions to Imine Derivatives and Ring-Forming Reactions. James D. Sunderhaus, Chris Dockendorff, and Stephen F. Martin. Tetrahedron 2009, 65, 6454. http://dx.doi.org/10.1016/j.tet.2009.05.009
- Discovery of μ-Opioid Selective Ligands Derived from 1-Aminotetralin Scaffolds Made via Metal-Catalyzed Ring-Opening Reactions. Chris Dockendorff, Shujuan Jin, Madeline Olsen, Mark Lautens, Martin Coupal, Lejla Hodzic, Kemal Payza, Christopher Walpole, and Miroslaw J. Tomaszewski. Bioorg. Med. Chem. Lett. 2009, 19, 1228. http://dx.doi.org/10.1016/j.bmcl.2008.12.095
- Aryne Diels-Alder Reactions with Acyclic Dienes: Scope and Diastereoselectivity. Chris Dockendorff, Stefan Sahli, Madeline Olsen, Ludovic Milhau, and Mark Lautens. J. Am. Chem. Soc. 2005, 127, 15028. http://dx.doi.org/10.1021/ja055498p