The objective of this research proposal is to develop new catalytic protocols for the direct C?H functionalization of aromatic compounds. Aromatic compounds are central motifs in the vast majority of therapeutics and simple methods for their further elaboration are always in demand. The goal of this research program is to generate new synthetic tools for biomedical researchers to be able to derivatize lead aromatic-containing therapeutics in order to assemble libraries of drug candidates for further evaluation. This proposal describes the use of organic dyes as catalysts to enable over a dozen new chemical transformations. The value of the proposed synthetic methods is the ability to utilize aromatics that are not pre-oxidized, allowing for greater flexibility in the types of aromatic structures that can be employed. We predict that this research program will enhance the synthetic capabilities of medicinal chemists to explore greater chemical space in the development of small molecule therapeutics.

Public Health Relevance

The objective of this research program is to invent new catalytic synthetic protocols of relevance to elaboration of aromatics present in medicinal agents. Using organic dyes that are designed to transform visible light energy and to chemical energy, new chemical reactions will be developed that have relevance to medicinal compounds.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM120186-03
Application #
9532241
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Lees, Robert G
Project Start
2016-09-20
Project End
2020-07-31
Budget Start
2018-08-01
Budget End
2019-07-31
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
McManus, Joshua B; Nicewicz, David A (2017) Direct C-H Cyanation of Arenes via Organic Photoredox Catalysis. J Am Chem Soc 139:2880-2883
Margrey, Kaila A; McManus, Joshua B; Bonazzi, Simone et al. (2017) Predictive Model for Site-Selective Aryl and Heteroaryl C-H Functionalization via Organic Photoredox Catalysis. J Am Chem Soc 139:11288-11299
Margrey, Kaila A; Levens, Alison; Nicewicz, David A (2017) Direct Aryl C-H Amination with Primary Amines Using Organic Photoredox Catalysis. Angew Chem Int Ed Engl 56:15644-15648