New method of synthesizing ketene acetals

Having your research on the cover of a prestigious journal is a milestone in a faculty member’s career—it’s something South Dakota State University assistant professor Rachel Willand-Charnley and undergraduate researcher Timothy Paris already have under their belts.

Willand-Charnley became a faculty member in SDSU’s Department of Chemistry in 2018 after completing postdoctoral research under the tutelage of renowned chemistry professor Carolyn Bertozzi at the University of California, Berkeley, and then at Stanford University.

Paris, a Rapid City native who graduated in May with a triple major in chemistry, biochemistry and psychology, is first author on the Willand-Charnley lab’s debut article, which is featured on the cover of the Feb. 5 issue of the Journal of Organic Chemistry. The cover was designed by Willand-Charnley and Topher Charnley, the lab’s resident graphic artist.

Willand-Charnley’s research combines her expertise in organic chemistry, glycobiology and cancer immunology. Her lab’s research involves developing new methods in organic chemistry and applying organic chemistry to understanding biological processes and solve biological problems, a field referred to as chemical biology. The lab’s research has applications in biotechnology and biomedicine.

Fulfilling research experience

Though Paris came to SDSU on a baseball scholarship, his interest in research led him to initiate a meeting with Willand-Charnley, his Organic Chemistry II professor. “I knew she would challenge me and provide good opportunities for collaboration and enriching conversations that would help me grow,” Paris said. From the beginning, the expectation was “we are going to do really impactful work that will make it into a good journal—and we accomplished our goal.”

After working in Willand-Charnley’s lab for a few months, Paris realized he did not have time for both research and baseball. After three semesters on the SDSU team, he made the difficult decision to step away from baseball. That experience was what he wrote about in the essay that earned him the prestigious Goldwater Scholarship. The Barry Goldwater Scholarship and Excellence in Education Foundation scholarship provided $7,500 for tuition and fees during his senior year.

“Tim is an outstanding researcher who took on the challenge I put before him of utilizing peroxides to synthesize ketene acetals, difficult substrates to synthesize,” Willand-Charnley said. “The inability to synthesize them in a facile manner is evident from the lack of available methodology in the literature.”

Making research a priority was “a good decision,” Paris said. “What makes the research work special is the amount of trust and independence Rachel has given me.” However, he pointed out, “I had to earn that through my own due diligence.” He delved into the literature and designed experiments that he then carried out with Willand-Charnley’s approval.

“She respects my opinion because I’ve earned it and done good work for her that was my own contribution,” he said.

Willand-Charnley agreed. “Tim operates at a postgraduate level and this is one component of his success. He took the research idea I presented to him and added to it in a substantive way. He did all the work, which is impressive.”

Paris continued, “Ketene acetals are a functional group that can be applied to a lot of reactions in organic chemistry. However, they are not very stable, so they are difficult to isolate. We used a specific selection of carbanions and peroxides to synthesize more stable, isolable ketene acetals.”

Willand-Charnley said, “Our method uses peroxides to synthesize a hard-to-reach target that will have utility downstream in pharmaceutical applications.”

Making connections

In addition to completing two more research articles, Paris, who is also a member of the Van D. and Barbara B. Fishback Honors College, has accepted a research associate position at Stanford University’s Medicinal Chemistry Knowledge Center. Beginning Aug. 2, Paris will work under the direction of senior research scientist Mark Smith, who leads the center. After this research experience, Paris plans to pursue M.D./Ph.D. degrees. 

Through his experience with Willand-Charnley, Paris has opportunities that he never anticipated. “Rachel offered me a foot in the door. I did my best to get papers published and to fill my resume with great things—and she introduced me to people she collaborated with at Stanford University,” he said.

Paris’s advice to other students: “There are a lot of opportunities at South Dakota State, you just have to go after them and make them happen.”