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Martin D. Burke

Martin D. Burke
Program
Beckman Young Investigators

Award Year
2008

Institution
University of Illinois Urbana-Champaign

Email:
burke@mail.scs.uiuc.edu

Website:
http://www.scs.uiuc.edu/chem/burke.html

Research Title:
Iterative Cross-coupling: A Simple Strategy for Generalizing and Automationg the Synthesis of Complex Small Molecules

Abstract:
Small molecules, including natural products and synthetic drug-like molecules, have seemi-ngly limitless potential tol promote advances in science and medicine. Ultimately, the degree to which this potential can be realized is a function of the simplicity, efficiency and flexibility with which these types of compounds can be synthesized in the laboratory. Modern peptide synthesis, involving the simple (and now routinely automated) iterative coupling of bifunctional amino acid building blocks, represents a benchmark in this regard. In sharp contrast, the laboratory synthesis of small molecules remains a relatively complex and non-systematized process. We herein propose a simple and highly modular strategy for making small molecules which is analogous to peptide synthesis and involves recursive carbon-carbon bond formation between bifunctional 'haloboronic acid' building blocks. Toward this end, we have newly discovered that the reactivity of a boronic acid can be reversibly attenuated via complexation with a trivalent ligand. We have also found that this phenomenon can enable syntheses of natural products that employ only one reaction to bring together a collection of easily synthesized, readily purified, and highly robust building blocks. The primary objective of this research proposal is to transform these promising preliminary, results into a general and automated process for the efficient and flexible construction of a broad range of complex small molecules. The impact on the start-of-the-art of small molecule synthesis will be substantial, ultimately making this powerful discovery engine accessible to the non-expert. Achieving this goal will broadly enable the more effective study and widespread utilization of this extraordinary class of compounds.


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