Issue Date: March 17, 2014
Arthur C. Cope Scholar Award: Jeffrey N. Johnston
Like many future scientists, Jeffrey N. Johnston’s childhood was full of opportunities to tinker. Only he didn’t quite recognize that at the time. “My father did a lot of heating and air-conditioning repair on the side,” he recalls. On weekends, he and his brother came along on their father’s rounds in the Cincinnati area. “I saw everything from the basement of an apartment complex to the roof of a pizza place,” Johnston, 42, says. Those weekends helping his dad work with pliers and pipe wrenches taught him how to be resourceful and handle unexpected problems as they surface. “I use those skills to this day,” says Johnston, the Stevenson Professor of Chemistry at Vanderbilt University.
That ingenuity has been a boon for catalysis, organic synthesis, and chemical biology. Johnston’s group is best known for developing chiral proton catalysts. These catalysts, which feature a protonated bis-amidine motif, use a polar ionic hydrogen bond to activate and position a substrate for a chemical transformation, much like the hydrogen bonds in certain enzymes. Johnston’s team has used the catalysts to make improvements to the aza-Henry reaction, a classic carbon-carbon bond formation.
His team also has developed a route to amides that proceeds in an unexpected way. Typically, amide bond formations require an electron-poor carbon source and electron-rich nitrogen source. But Johnston’s umpolung amide synthesis uses an electron-rich carbon source and electron-poor nitrogen source instead. “This is not simply a mechanistic curiosity, but instead a great opportunity to solve long-standing problems in peptide synthesis,” such as enantioselectivity, says Johnston’s Vanderbilt colleague Ned A. Porter.
Johnston’s group uses his chemistry to cheaply build molecular probes and drug candidates. These include a lead compound for treating Chagas disease, a parasitic infection endemic in developing regions, and nutlin-3, a compound that blocks a key protein-protein interaction in cancer. “Despite tremendous interest in the nutlins as tools and potential therapeutics, their availability has been limited to a single commercial source at high cost,” says Franklin A. Davis of Temple University.
The mark of those and all of Johnston’s syntheses is efficiency, says Daniel Romo of Texas A&M University. Most of Johnston’s routes clock in at under 15, or even under 10, steps, Romo notes.
Johnston began thinking about complexity and efficiency in graduate school at Ohio State University, working for Leo A. Paquette. “Leo is an absolute master of creating structural complexity in a flask,” Johnston says. Once he earned his Ph.D., Johnston completed a National Institutes of Health postdoctoral fellowship with David A. Evans at Harvard University. He began his independent career at Indiana University and moved to Vanderbilt in 2006.
He has earned numerous honors and awards. He is a fellow of the American Association for the Advancement of Science and was recently named a Japan Society for the Promotion of Science fellow.
Johnston says his next goal is to bring more tools of enantioselective catalysis to peptide synthesis. “One trick of this job seems to be to not look back, and worry mostly about what’s on tomorrow’s agenda,” he says.
- Chemical & Engineering News
- ISSN 0009-2347
- Copyright © American Chemical Society