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.
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|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|
|Joshi-Pangu, Amruta; Biscoe, Mark R (2012) The Use of Tertiary Alkylmagnesium Nucleophiles in Ni-Catalyzed Cross-Coupling Reactions. Synlett 23:1103-1107|
|Joshi-Pangu, Amruta; Ma, Xinghua; Diane, Mohamed et al. (2012) Palladium-catalyzed borylation of primary alkyl bromides. J Org Chem 77:6629-33|
|Joshi-Pangu, Amruta; Ganesh, Madhu; Biscoe, Mark R (2011) Nickel-catalyzed Negishi cross-coupling reactions of secondary alkylzinc halides and aryl iodides. Org Lett 13:1218-21|
|Joshi-Pangu, Amruta; Wang, Chao-Yuan; Biscoe, Mark R (2011) Nickel-catalyzed Kumada cross-coupling reactions of tertiary alkylmagnesium halides and aryl bromides/triflates. J Am Chem Soc 133:8478-81|