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.
*Paper based on a presentation at the 24th International Symposium on the Chemistry of Natural Products and the 4th International Congress on Biodiversity, held jointly in Delhi, India, 26-31 January 2004. Other presentations are published in this issue, pp. 1-344.