We are engaged in the first systematic efforts to exploit catalytic ketone/unsaturated moiety coupling via C-C activation. Our objective, in the proposed funding period, is to develop a "Cut and Sew" strategy for the efficient synthesis of bridged/fused ring systems via catalytic C-C activation, which includes 1) regular "Cut and Sew": Rh- or Co-catalyzed intramolecular carboacylation with both strained and unstrained cyclic ketones;2) decarbonylative "Cut and Sew": catalytic intramolecular couplings between cyclic ketones and unsaturated moieties with CO extrusion. The research proposed is expected to provide a general and unified strategy to build complex skeletons, found in numerous natural products and drugs, from simple starting materials.

Public Health Relevance

Complex ring structures exist in over 60% of natural products and pharmaceutical compounds, and these scaffolds generally play key roles in their biological activity. However, chemical synthesis of these ring systems proves challenging, and current approaches need to be improved. Employing our recently developed C-C activation strategy, the outlined proposal provides rapid/general access to the core skeletons of various biologically important molecules in a catalytic and byproduct-free manner, which, in turn, would significantly expedite the synthesis of these molecules and ultimately accelerate drug discovery.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01GM109054-02
Application #
8744633
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Lees, Robert G
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Texas Austin
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
City
Austin
State
TX
Country
United States
Zip Code
78712