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Pure Appl. Chem., 2005, Vol. 77, No. 1, pp. 163-178

Toward the library generation of natural product-like polycyclic derivatives by stereocontrolled diversity-oriented synthesis

P. Arya*, S. Quevillon, R. Joseph, C.-Q. Wei, Z. Gan, M. Parisien, E. Sesmilo, P. T. Reddy, Z.-X Chen, P. Durieux, D. Laforce, L.-C. Campeau, S. Khadem, S. Couve-Bonnaire, R. Kumar, U. Sharma, D. M. Leek, M. Daroszewska and M. L. Barnes

Chemical Biology Program, Steacie Institute for Molecular Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, Ontario K1A 0R6, Canada

Abstract: Due to the growing interest in small molecules that could help in understanding protein–protein interactions based on signal transduction, the demand for the generation of small-molecule libraries that are inspired by bioactive natural products has grown significantly. Many of these pathways are highly complex and present tremendous challenges with the use of classical tools. A rapid access to natural product-like small molecules having structural complexity and diversity is crucial for systematically dissecting the functions of complex protein networking and understanding cell signaling pathways. The complex nature, the three-dimensional architecture, and the number of protein binding functional groups presented in three-dimensional arrays are some of the attractive features to incorporate in small-molecule chemical probes to be used as modulators of protein function.