We aim to produce non-racemic biologically active molecules by employing optically active organometallic nucleophiles in transition metal-catalyzed carbon-carbon bond- forming reactions. 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, an extended to the use of optically active tertiary nucleophiles. Alkylboron and alkyl azastannatrane reagents constitute the main nucleophiles involved in this study. Although the major focus of this work is on palladium- and nickel-catalyzed systems, the use of copper and silver catalysis will also be investigated. Our stereoretentive cross- coupling reactions will be extended to the construction of carbon-heteroatom bonds 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
Research Enhancement Award (SC1)
Project #
1SC1GM110010-01
Application #
8667099
Study Section
Special Emphasis Panel (ZGM1-TWD-X (SC))
Program Officer
Lees, Robert G
Project Start
2014-04-01
Project End
2018-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
1
Fiscal Year
2014
Total Cost
$368,890
Indirect Cost
$118,890
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