03/09/17 - 9:45 AM to 11:00 AM
Dow Lecture Series: Professor Jeffrey N. Johnston
Dow Lecture Series
"New Catalysts, Methods, and Strategies for Therapeutic Development and On-Demand Natural Product Total Synthesis"
Small molecules are a mainstay of drug development, o ering structural and functional topologies to precisely occupy receptor pockets. Increasingly complex protein-protein interactions demand great- er breadth of structural and stereochemical complexity, as well as size, within a discrete compound collection. Furthermore, the incorporation of uorine into small molecules can provide directed con- formational bias, enhance desirable drug like properties, and improve metabolic stability. All of these features are meaningful only when they are at arm’s reach – essentially on-demand – such that atten- tion is focused predominantly on the greater issues of potency and selectivity. Tools that enhance the immediacy of availability and acquisition are in high demand.
Chiral proton catalysis using Bis(AMidine) (BAM) ligands has generalized access to numerous types of enantioenriched, functionally complex secondary amines. Now readily available, this feedstock is the platform for new reaction development that provides unfettered access to a broad range of enantiopure products, including α-amino amides and heterocycles. Our latest work in this area will be described, with an emphasis on the stereocontrolled formation of carbon-heteroatom bonds (C- O, C-N, C-F), unnatural amino acid-containing peptides, and depsipeptides with macrocycles up to 60-atoms in size.
Professor Johnston is interested in the development of new reactions and reagents for natural product total synthesis. His research group has contributed a variety of new reactions to the chemist's arsenal, including free radical-mediated aryl and vinyl amination, the Brønsted acid-catalyzed aza-Darzens reaction, and a new acid catalyzed olefin aminoacyloxylation reaction. They also apply these reactions to the targets that inspired them. In addition, they have advanced the concept and first embodiment of chiral proton catalysis—polar ionic hydrogen bond catalysis; explored Umpolung Amide Synthesis (UmAS), and its use to prepare α-amino acids, and their polymers—peptides—using fully enantioselective means; and developed ongoing collaborative projects in organometallic catalysis that target reactions not amenable to protic acid catalysis, and the broad area of medicinal chemistry.