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Contact Information

Office: WEL: 5.334
Phone: 512-471-3915

Lab

Office: WEL 5.426
Phone: 512-232-2168

Stephen F. Martin

sfmartin@mail.utexas.edu

Professor, Faculty
M. June and J. Virgil Waggoner Regents Chair in Chemistry



Research Group

Martin Research Group



Education

BS, University of New Mexico, 1968
PhD, Princeton University, 1972

Alexander von Humboldt Stipendiat, Institut fur Organische Chemie der Universitat Munchen (1972-73)



Awards

International Society of Heterocyclic Chemistry (ISHC) Senior Award, 2013

Fellow of American Association for the Advancement of Science, 2005
Wyeth Research Award, 2003
Japan Society for the Promotion of Science Award, 2001
Arthur C. Cope Scholar Award, 1996
Alexander von Humboldt Prize, 1995



Affiliations

Institute for Cellular and Molecular Biology; Waggoner Center for Alcohol & Addiction Research



Natural Product Synthesis


The focus of current research is upon inventing and developing general tactics and strategies for the synthesis of natural and unnatural products of biological or structural interest. A variety of architecturally complex alkaloids, acetogenins, and terpenes serve as targets of opportunity to discover novel chemistry that will have general utility. For example, we are developing and applying new aspects of Diels-Alder and hetero Diels-Alder cycloadditions as well as vinylogous Mannich and ring closing metathesis reactions to elaborate functionalized nitrogen and oxygen heterocycles as key steps in formulating approaches to a diverse array of natural products. In addition to these strategy level constructions, useful synthetic processes, including domino and multicomponent reactions, are being developed to fill voids in available methodology. The biological activity and profiles of selected compounds are studied with the goal of identifying novel probes of biological function and pathways associated with cancer, neurological disorders and other diseases.

 

Molecular Recognition in Protein-Ligand Interactions


The design and synthesis of small molecules that exhibit high affinities and specificities for selected proteins is a key step in the process of identifying potential enzyme inhibitors and receptor antagonists or agonists. Toward this goal, we have adopted a unique, multidisciplinary approach wherein synthetic organic chemistry, microcalorimetry, protein crystallography, NMR spectroscopy, surface plasmon resonance, and computational chemistry are integrated in systematic studies to investigate explicitly how specific variations in ligand structure affect energetics, nonbonded interactions, dynamics, and kinetics in protein-ligand interactions. The focus of current studies is upon investigating the detailed effects of introducing conformational constraints and nonpolar substituents into small molecules that bind to SH2 domains, hepatitis C viral protease, and several other proteins of biological or medicinal interest.

 



Representative Publications

S. F. Martin and J. H. Clements, Annu. Rev. Biochem. 2013, 82, 267. "Correlating Energetics and Structure in Protein-Ligand Interactions: Paradigms and Paradoxes."

 

B. A. Granger, I. T. Jewett, J. D. Butler, B. Hua, C. E. Knezevic, E. I. Parkinson, P. J. Hergenrother, and S. F. Martin, J. Am. Chem. Soc. 2013, 135, 12984. "Synthesis of (±)-Actinophyllic Acid and Analogs: Applications of Cascade Reactions and Diverted Total Synthesis."

 

Z. Bian, C. C. Marvin, and S. F. Martin, J. Am. Chem. Soc. 2013, 135, 10886. "Enantioselective Total Synthesis of (–)-Citrinadin A and Revision of its Stereochemical Structure."

 

C. Fang, C. S. Shanahan, D. H. Paull, and S. F. Martin, Angew. Chem. Int. Ed. 2012, 51, 10596. "Enantioselective Formal Total Syntheses of Didehydrostemofoline and Isodidehydrostemofoline via a Novel Catalytic Dipolar Cycloaddition Cascade."


D. H. Paull, C. Fang, J. R. Donald, A. D. Pansick, and S. F. Martin, J. Am. Chem. Soc. 2012, 134, 11129. "Bifunctional Catalyst Promotes Highly Enantioselective Bromolactonizations to Generate Stereogenic C–Br Bonds."


J. Donald, B. Granger, S. Hardy, J. Sahn and S. F. Martin, Heterocycles 2012, 84, 1089 "Applications of Multicomponent Assembly Processes to the Facile Syntheses of Diversely Functionalized Nitrogen Heterocycles."


J. M. Myslinski, J. E. DeLorbe, J. H. Clements, and S. F. Martin, J. Am. Chem. Soc. 2011, 133, 18518. "Protein-Ligand Interactions: Thermodynamic Effects of Increasing Nonpolar Surface Area."

 

J. H. Clements, J. E. DeLorbe, M. G. Teresk, A. P. Benfield, H. R. Plake, L. E. Millspaugh, and S. F. Martin, J. Am. Chem. Soc. 2009, 131, 16758. "Thermodynamic and Structural Effects of Conformational Constraints in Protein-Ligand Interactions. Entropic Paradoxy Associated with Ligand-Preorganization."