Advances in 21st century medicine have greatly impacted society, but a serious need persists for new therapeutics that either exploit known biological processes or possess novel mechanisms of action. The development of new, selective, and enabling chemical methodology to drive the rapid investigation of the reactivity and biological activity of natural products and related probes is vital to understanding their mechanism of action and developing new therapeutics for the treatment and/or prevention of disease. A primary goal of our research program is to discover and develop new cooperative catalytic, stereoselective transformations that facilitate the highly efficient construction of valuable materials. The new methods advanced in this proposal have a) significant and highly encouraging preliminary results, and b) been inspired by bioactive molecules/natural products that will subsequently facilitate the efficient construction of these targets and potential applications towards clinical endpoints. The innovative cooperative catalytic strategies we are pursuing will power investigations of biological processes relevant to the discovery of new potential therapies and strategies that generate the targeted bioactive molecules while providing broad solutions to synthesizing related families of compounds. The specific goals of this research are: a) the exploration of new, cooperative carbene catalyzed processes, b) the development of stereoselective catalytic carbocation-driven transformations, c) the investigation of Lewis acid-catalyzed ?-Umpolung type radical reactions, and d) the merger of photocatalytically-generated reactivity with biocatalysis. We anticipate that these research activities will fundamentally advance human health by providing innovative tactics and strategies to access many important classes of health relevant compounds.

Public Health Relevance

The broad goal of this research program is the continued successful development and application of cooperative catalysis concepts for asymmetric synthesis to move the fields of chemistry and biology forward by providing unconventional strategies and address key challenges involving catalysis compatibility, selectivity and novelty. We are specifically investigating innovative carbene catalyzed processes with different catalysis modes, carbocation driven processes, and merging photocatalysis with biocatalysis. New chemical method development integrated with target synthesis is an essential activity to access high value molecules that drive new chemical probe creation and potential therapeutics that are critical for new knowledge and medical advances.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
1R35GM136440-01
Application #
9931752
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Yang, Jiong
Project Start
2020-06-01
Project End
2025-05-31
Budget Start
2020-06-01
Budget End
2021-05-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
160079455
City
Chicago
State
IL
Country
United States
Zip Code
60611