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Dr. Dionicio Siegel
Synthetic Organic Chemistry, Medicinal Chemistry, and Molecular Pharmacology
Dionicio Siegel, Ph.D.
Skaggs School of Pharmacy and Pharmaceutical Sciences
Research Summary: Synthesis Applied to Drug Development
Our group develops synthetic routes to natural products that promote neuronal survival and regeneration. This provides the basis for subsequent investigations into the mechanisms of action of the compounds as well as optimization of the natural products’ biological performance through medicinal chemistry. In addition, we evaluate compounds for the ability to promote neuronal regeneration in vivo through the use of injury models in C. elegans and in collaboration with academic and industrial research groups using different models of injury.
We have an ongoing synthetic methodology program developing broadly applicable methods for arene oxidation. We have discovered the reaction of phthaloyl peroxide with aromatic compounds installs oxygen a single time. The reaction has enabled the hydroxylation of a wide variety of arenes providing the corresponding phenols and, importantly, the reaction is compatible with a large number of functional groups.
Through collaborative efforts with research groups in different disease areas we optimize compounds that originate in their laboratories for pharmacokinetic and pharmacodynamics properties. We also help prepare novel molecular probes to decipher the mechanisms of action of these compounds.
B.A. Chemistry (1997) Reed College; Ph.D. Chemistry (2003) Harvard University; Postdoctoral Studies in Molecular Pharmacology (2003-2007) Memorial Sloan Kettering Cancer Center
Awards and Honors:
Institute Fellowship, California Institute of Technology (1997-1998); Upjohn-Pharmacia Fellow (1998); Congressionally Directed Medical Research Program Postdoctoral Fellowship Award (2005-2007); College of Natural Science Teaching Excellence Award (2010); The University of Texas System Reagents’ Outstanding Teaching Award (2010); College of Natural Sciences Outreach Excellence Award (2011); National Science Foundation CAREER Award (2012-2017)
Director of Texas Shamans, 2008-2013.
Key Contributions to Pharmaceutical Sciences
- Developed synthetic routes to natural products with established abilities to promote neuronal growth and regeneration.
- Determined biological targets of natural products with unknown mechanism of action.
- Developed a new synthteic method for the conversion of arenes to phenolic compounds tolerant of diverse functionality.
Selected Recent Publications (view more)
- Axelrod, A et al. (2013). Syntheses of Xanthofulvin and Vinaxanthone, Natural Products Enabling Spinal Cord Regeneration. Angew. Chem. Int. Ed. 52:3421-3424
- Yuan, C et al. (2013). Syntheses of (+)-Complanadine A and Lycodine Derivatives by Regioselective [2+2+2] Cycloadditions. J. Org. Chem. 78:5647-5668
- Yuan, C et al. (2013). Metal-Free Aromatic C-H Oxidation Through a Reverse Rebound Mechanism. Nature 499:192-196
- Zlotkowski, K et al. (2013). Small-Molecule Mechanism of Action Studies in Caenorhabditis elegans. ChemBioChem 14:2338-2344
- Johnson, T et al. (2014). Complanadine A, a selective agonist for the mas-related G protein-coupled receptor X2. Bioorg. Med. Chem. Lett. 15:3512-3515.
Potential Collaborative Programs with the Pharmaceutical Industry
- Design and synthesis of compounds predicted to have improved pharmacokinetic/pharmacodynamic
- Development of synthetic routes affording gram to decagram access to preclinical agents
- Direct synthesis of phenolic metabolites from drugs for toxicology and related testing
- Creation of convergent synthetic routes to rapidly access chemically edited analogs
- Training opportunities for synthetic chemists