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Harry G. Day Chair and Professor, Chemistry Department

David R. Williams received his B.S. degree (Magna Cum Laude) at St. Lawrence University (Canton, New York). He went on to graduate studies at the Massachusetts Institute of Technology and was awarded the Ph.D. in organic chemistry in 1976 under the direction of Professor George Büchi. Subsequently, he was awarded the National Institutes of Health Postdoctoral Fellowship for studies at Harvard University with Professor E. J. Corey (Nobel laureate), and also served as an NIH Fellow at Harvard under the mentorship of Professor R. B. Woodward (Nobel laureate). Dr. Williams began his academic career at IU in 1980. His research has resulted in over 100 scholarly publications. To date, one hundred graduate students and postdoctoral associates have studied in his laboratories.

Dr. Williams' research interests lie in the development of methodologies and strategies for the total synthesis of biologically active natural products. The Williams' laboratories have made leading contributions of synthetic chemistry in areas of marine natural products, including macrocycles, antibiotics, and alkaloids. To date, these efforts have described new pathways to approximately 40 complex natural product structures of importance as potential therapeutic agents to advance treatments for cancer, as well as other diseases.

Research

The research efforts of our laboratories involve synthetic organic chemistry in its very broadest sense.  We undertake fundamental studies in the chemistry of recently discovered, biologically active natural products, such as terpenes, alkaloids, and macrocyclic antibiotics, which are structurally unique and thus far unexplored.

Generally, our efforts are focused on the preparation of complex substances which have pharmacological significance.  Current studies are directed toward new agents for treatment of cardiovascular disorders and cancers. 

Our studies are designed to produce new synthetic methodology and new reagents that expand the basic body of knowledge for designing organic syntheses and understanding chemical reactions.  One objective of these studies is to develop expertise for the rapid and efficient assembly of complex arrangements of stereochemistry and polyfunctionality.

Previous successes have led to methods for the stereocontrolled formation of highly substituted tetrahydrofurans and related heterocyclic systems.  New techniques for the preparation of medium-sized carbocyclic rings, and the transannular chemistry of such systems, have fueled our interest in terpenoids of marine origin.  Enantioselective methodology toward the development of organometallic reagents has continued to be a primary objective, particularly for synthesis of complex acyclic and macrocyclic antibiotics.

In our laboratories, chemical discovery is driven by the anticipated challenges presented by the unique molecular architecture of the targeted natural products.  The finest examples of our achievements are intended to express the art of organic chemistry, as well as the basis for fundamental information of chemical selectivity and synthetic strategy.  A number of natural products currently under investigation are illustrated below.

We use advanced nuclear magnetic resonance techniques and mass spectrometry on a daily basis, as well as flash and liquid chromatography and X-ray crystallographic analysis.  Graduate students conduct research on well-defined, individual projects involving a wide range of reactions and types of molecules.  My goal, as an educator and mentor, is to provide a broad base of experiences to enhance the knowledge and creativity of the future scientist.

Publications

D. R. Williams, A. A. Kiryanov, U. Emde, M. P. Clark, M. A. Berliner and J. T. Reeves, Studies of Stereocontrolled Allylation Reactions for the Total Synthesis of Phorboxazole A, Proceedings of the National Academy of Sciences, 101, 12058–12063, 2004.  PMC514434

D. R. Williams, D. C. Kammler, A. F. Donnell and W. R. F. Goundry, Total Synthesis of (+)-Apiosporamide:  Assignment of Relative and Absolute Configuration, Angew. Chem. Int. Ed. 44, 6715–6718, 2005.

D. R. Williams and M. W. Fultz, 1-Alkoxyallene as an Effective Precursor for Regio- and Stereocontrolled Allylation Reactions with Aliphatic Aldehydes via Bis-Stannylation, J. Am. Chem. Soc. 127, 14550–14551, 2005.

D. R. Williams and K. Shamim, Studies Toward the Synthesis of Kendomycin, Org. Lett. 7, 4161–4164, 2005.

D. R. Williams, Á. I. Morales-Ramos and C. M. Williams, Reactivity Studies of 3,3-Bis(trimethylsilyl)-2-methyl-1-propene in Lewis Acid-Catalyzed Allylation Reactions, Org. Lett. 8, 4393–4396, 2006.

D. R. Williams, J. T. Reeves, P. P. Nag, W. H. Pitcock, Jr. and M.-H. Baik, Studies of the Generation and Pericyclic Behavior of Cyclic Pentadienyl Carbanions.  Alkylation Reactions As an Efficient Route to Functionalized cis-Bicyclo[3.3.0]octenes, J. Am. Chem. Soc. 128, 12339–12348, 2006.

D. R. Williams, L. A. Robinson, C. R. Nevill and J. P. Reddy, Strategies for the Synthesis of Fusicoccanes via Nazarov Reactions of Dolabelladienones. Total Synthesis of (+)-Fusicoauritone, Angew Chem. Int. Ed. 46, 915–918, 2007.  PMC2924807

D. R. Williams, P. P. Nag and N. Zorn, The Development of Strategies for the Synthesis of Peloruside A – a Novel Antitumor Agent, Current Opinion in Drug Discovery and Development, 11, 251–271, 2008.  PMC2693484

D. R. Williams, M. J. Walsh, C. D. Claeboe, and N. Zorn, Studies for the Synthesis of Marine Natural Products, Pure Appl. Chem. 81, 181–194,2009.  PMC2814370

D. R.  Williams, M. J. Walsh, and N. A. Miller, Studies of Xenicane Diterpenes.  A Stereocontrolled Total Synthesis of 4-Hydroxydictyolactone, J. Am. Chem. Soc. 131, 9038–9045, 2009. 

D. R. Williams, M. W. Fultz, T. E. Christos, and J. S. Carter, A General Preparation of (Z)-1-Fluorostilbene Derivatives for the Design of Conformationally Restricted Peptidomimetics, Tetrahedron Lett. 51, 121–124, 2010. 

D. R. Williams and L. Fu, General Methodology for the Preparation of 2,5-Disubstituted-1,3-Oxazoles, Org. Lett. 12, 808–811, 2010. 

D. R. Williams and A. A. Shah, Regioselective Formation of 1,1-Disubstituted Allenylsilanes via Cross-Coupling Reactions of 3-Tri-n-butylstannyl-1-trimethylsilyl-1-propyne, Chem. Commun. 46, 4297–4299, 2010. 

D. R. Williams and L. Fu, Efficient Suzuki and Stille Reactions for Regioselective Strategies of Incorporation of the 1,3-Oxazole Heterocycle:  Mild Desulfonylation for the Synthesis of C-4 and C-5 Monosubstituted Oxazoles, Synlett 1641–1646, 2010. 

D. R. Williams, S. V. Plummer and S. Patnaik, Studies for the Enantiocontrolled Preparation of Substituted Tetrahydropyrans:  Applications for the Synthesis of Leucascandrolide A Macrolactone, Tetrahedron, 67, 5083–5097, 2011.

Awards

• Indiana University Distinguished Faculty Research Lecturer Award, 2007-2008
• Edward Leete Award of the American Chemical Society, 2005
• Fellow, American Association for the Advancement of Science, 2004
• Tracy M. Sonneborn Award, 2002
• Harry G. Day Chair, Department of Cheminstry, Indiana University, 2001
• Indiana University Teaching Excellence Recognition Award, 2000
• Merck Faculty Development Award, 1996
• Alfred P. Sloan Fellow, 1983

Highlights