Where discoveries are delivered.℠

External Resources:

Dionicio Siegel

Synthetic Organic Chemistry, Medicinal Chemistry, and Chemical Biology

Dionicio Siegel

Dionicio Siegel, Ph.D.

Associate Professor
Skaggs School of Pharmacy and Pharmaceutical Sciences

Email
drsiegel@ucsd.edu

Phone
(858) 822-3666


Research Summary: Natural Product Synthesis, Oxidation-Based Reaction Development, and Molecular Pharmacology

Our research group focuses on the development of synthetic routes to natural products that promote regeneration. These synthetic routes provide the basis for subsequent investigations into the modes of action of the select compounds. In addition, the established synthetic routes provide avenues for the optimization of the natural products’ biological performance through medicinal chemistry. Concurrent with these studies we evaluate the 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 animal models of neuronal injury.

We also 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, directly into the parent molecule and selectively into arenes. 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. Relevant to drug development and toxicology this reaction provides a novel method for the chemical synthesis of metabolites directly from preclinical agents.

Academic Achievements

Education: 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, California Institute of Technology (1998); Congressionally Directed Medical Research Program Postdoctoral Fellowship Award (2005-2007); College of Natural Science Teaching Excellence Award, The University of Texas at Austin (2010); The University of Texas System Reagents’ Outstanding Teaching Award (2010); College of Natural Sciences Outreach Excellence Award, The University of Texas at Austin (2011); National Science Foundation CAREER Award (2012-2017); Aldrich Lecturer, Yale University (2013)

Leadership Experience: 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

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

  • 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.