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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Pilot Research Project (SC2)
Project #
1SC2GM096932-01
Application #
8078467
Study Section
Special Emphasis Panel (ZGM1-MBRS-X (CH))
Program Officer
Lees, Robert G
Project Start
2011-07-01
Project End
2014-04-30
Budget Start
2011-07-01
Budget End
2012-04-30
Support Year
1
Fiscal Year
2011
Total Cost
$138,690
Indirect Cost
Name
City College of New York
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
603503991
City
New York
State
NY
Country
United States
Zip Code
10031
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
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; 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
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