Photochemical synthesis represents an exciting frontier for drug discovery and for biomedical research. The ability of small, structurally complex organic molecules to interact with biomolecules and perturb their behavior is at the heart of modern molecular medicine and chemical biology. The discovery of new drugs and biological probes with new properties, therefore, relies critically upon the synthesis of new molecules with unprecedented structures. Photochemistry has long been an underdeveloped technique in chemical synthesis, in part because the irradiation of organic molecules with light results in the generation of highly reactive, high-energy species that can react indiscriminately and unproductively. We are investigating the ways in which addition of various reagents to photochemical reactions can control these photogenerated intermediates in diverse ways. In this proposal, we describe two Specific Aims to study how these reagents can result in powerful new bond forming methods.
Aim 1. We are exploring the ability of chiral catalysts to control the stereochemistry of photochemical reactions.
Aim 2. We are exploring the ability of copper oxidants to enable the installation of functional groups onto simple unfunctionalized organic scaffolds. These methods enable chemical transformations that cannot otherwise be accomplished using conventional, non-photochemical technologies. Thus, we expect that the results of our research will have significant impacts both in fundamental academic chemical research and on the ability of biomedical scientists to synthesize and discover the next generation of life-saving drugs.

Public Health Relevance

The discovery of new, life-saving drugs requires chemists to be able to synthesize new molecular structures. The research described in this proposal will use light to produce highly energetic reactive intermediates and then utilize various strategies to control their subsequent reactions. We expect the impacts of this research to have both fundamental scientific impacts and practical enabling impacts in modern drug discovery.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM095666-10
Application #
9843137
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Yang, Jiong
Project Start
2010-12-01
Project End
2022-11-30
Budget Start
2019-12-01
Budget End
2020-11-30
Support Year
10
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Amador, Adrian G; Sherbrook, Evan M; Lu, Zhan et al. (2018) A general protocol for radical anion [3 + 2] cycloaddition enabled by tandem Lewis acid photoredox catalysis. Synthesis (Stuttg) 50:539-547
Reed, Nicholas L; Herman, Madeline I; Miltchev, Vladimir P et al. (2018) Photocatalytic Oxyamination of Alkenes: Copper(II) Salts as Terminal Oxidants in Photoredox Catalysis. Org Lett 20:7345-7350
Pitre, Spencer P; Yoon, Tehshik P; Scaiano, Juan C (2017) Titanium dioxide visible light photocatalysis: surface association enables photocatalysis with visible light irradiation. Chem Commun (Camb) 53:4335-4338
Miller, Zachary D; Lee, Byung Joo; Yoon, Tehshik P (2017) Enantioselective Crossed Photocycloadditions of Styrenic Olefins by Lewis Acid Catalyzed Triplet Sensitization. Angew Chem Int Ed Engl 56:11891-11895
Lin, Shishi; Lies, Shane D; Gravatt, Christopher S et al. (2017) Radical Cation Cycloadditions Using Cleavable Redox Auxiliaries. Org Lett 19:368-371
Pitre, Spencer P; Scaiano, Juan C; Yoon, Tehshik P (2017) Photocatalytic Indole Diels-Alder Cycloadditions Mediated by Heterogeneous Platinum-Modified Titanium Dioxide. ACS Catal 7:6440-6444
Amador, Adrian G; Sherbrook, Evan M; Yoon, Tehshik P (2016) Enantioselective Photocatalytic [3 + 2] Cycloadditions of Aryl Cyclopropyl Ketones. J Am Chem Soc 138:4722-5
Skubi, Kazimer L; Blum, Travis R; Yoon, Tehshik P (2016) Dual Catalysis Strategies in Photochemical Synthesis. Chem Rev 116:10035-74
Yoon, Tehshik P (2016) Photochemical Stereocontrol Using Tandem Photoredox-Chiral Lewis Acid Catalysis. Acc Chem Res 49:2307-2315
Blum, Travis R; Miller, Zachary D; Bates, Desiree M et al. (2016) Enantioselective photochemistry through Lewis acid-catalyzed triplet energy transfer. Science 354:1391-1395

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