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Chemistry A350B
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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 group 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 antibiotics, which are structurally unique and thus far unexplored.

Generally, our efforts are focused on the preparation of complex substances of pharmacological significance. Present studies are directed toward new agents for treatment of cardiovascular disorders and neoplastic diseases, as well as new antibiotics.

These efforts are designed to produce new synthetic methodology, expanding the basic body of knowledge for designing organic syntheses and understanding chemical reactions to allow formation 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 or macrocyclic antibiotics.

In our laboratories, chemical discovery is driven with the anticipated, and sometimes unanticipated, challenges presented by the unique molecular architecture of the targeted natural products, such as those in the accompanying illustrations. The finest examples of our achievements are intended to express the art of organic chemistry, as well as the basis for new fundamental information of chemical selectivity and synthetic strategy.

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 compounds. This provides a very broad base of experiences to enhance the knowledge and creativity of the future scientist.

Publications

D. R. Williams and W. S. Kissel, Total Synthesis of (+)-Amphidinolide J, J. Am. Chem. Soc. 120, 11198–11199, 1998.

D. R. Williams, D. A. Brooks and M. A. Berliner, Total Synthesis of (–)-Hennoxazole A, J. Am. Chem. Soc. 121, 4924–4925, 1999.

D. R. Williams, B. J. Myers and L. Mi, Total Synthesis of (–)-Amphidinolide P, Org. Lett, 2, 945–948, 2000.

D. R. Williams and R. A. Turske, The Construction of 4-Hydroxy-2-Pyridinones. Total Synthesis (+)-Sambutoxin. Org. Lett. 2, 3217–3220, 2000.

D. R. Williams, G. S. Cortez, S. L. Bogen and C. M. Rojas, Total Synthesis of Lankacyclinol, Angew. Chemie, Intl. Ed. 39, 4612–4615, 2000.

D. R. Williams and K. G. Meyer, Total Synthesis of (+)-Amphidinolide K, J. Am. Chem. Soc. 123, 765–767, 2001.

D. R. Williams, M. G. Fromhold and J. D. Earley, Total Synthesis of (–)-Stemospironine, Org. Lett. 3, 2721–2724, 2001.

D. R. Williams and R. W. Heidebrecht, Jr., Total Synthesis of (+)-4,5-Deoxyneodolabelline, J. Am. Chem. Soc. 125, 1843–1850, 2003.

D. R. Williams, S. V. Plummer and S. Patnaik, Formal Synthesis of Leucascandrolide A, Angew. Chem. Int. Ed. 42, 3934–3938, 2003.

D. R. Williams, K. Shamim, J. P. Reddy, G. A. Amato and S. M. Shaw, Total Synthesis of (–)-Stemonine, Org. Lett. 5, 3361–3364, 2003.

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.

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, 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.

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