We aim to develop new, general methods for obtaining non-racemic biologically-active molecules using transition metal-catalyzed carbon-carbon bond-forming reactions that employ configurationally-stable, optically-active nucleophiles. By establishing the stereogenic center prior to the formation of the final desired bond, the rapid preparation of diverse libraries of single-enantiomer drug candidates for use in biologic assays will be achievable. The use of optically-active secondary nucleophiles will be initially explored in alkyl-aryl cross-coupling reactions and extended to alkyl-alkyl cross-coupling reactions in order to maximize access to chiral structural motifs that are currently inaccessible but are of biological or pharmaceutical interest.
Our proposed research focuses on the development of new, general methods to prepare diverse libraries of biologically-active molecules for testing as drug candidates. We aim to devise new drug discovery techniques that permit rapid access to common, high- demand molecular architectures predictably, safely, and inexpensively.
|Li, Ling; Zhao, Shibin; Joshi-Pangu, Amruta et al. (2014) Stereospecific pd-catalyzed cross-coupling reactions of secondary alkylboron nucleophiles and aryl chlorides. J Am Chem Soc 136:14027-30|
|Li, Ling; Wang, Chao-Yuan; Huang, Rongcai et al. (2013) Stereoretentive Pd-catalysed Stille cross-coupling reactions of secondary alkyl azastannatranes and aryl halides. Nat Chem 5:607-12|