Assistant Professor of Chemistry Jessica Kisunzu recently published two articles, “A Benzyne Insertion Approach to Hetisine-Type Diterpenoid Alkaloids: Synthesis of Cossonidine (Davisine)” and “Conformational Analysis of a Peptidic Catalyst,” in the Journal of the American Chemical Society.
“My research at Colorado College incorporates my interests in benzyne chemistry as well as the computational analysis of molecular structure and properties,” says Kisunzu, who joined CC’s Department of Chemistry and Biochemistry in the fall of 2017. “Students in my lab have the opportunity to make and study benzynes and related compounds, with the goal of developing new methods and applications.”
The research in the first article, “A Benzyne Insertion Approach to Hetisine-Type Diterpenoid Alkaloids: Synthesis of Cossonidine (Davisine)” began when Kisunzu was in graduate school at the University of California, Berkeley, and working with the Sarpong group there. Plants in the monkshood and larkspur family (Aconitum, Delphinium, and Consolida genera) contain numerous chemical compounds called diterpenoid alkaloids, a term that refers to the structural properties of these compounds as well as the basic starting materials that nature uses to make them. Kisunzu notes that “many diterpenoid alkaloids have biological activity, and some have been studied in relation to relieving pain, inflammation, or arrhythmia. In addition to a broad range of activity, diterpenoid alkaloids also have very complex structures.”
The Sarpong group at the University of California, Berkeley was interested in the synthesis and study of this family of molecules, she says. “The focus of the reported research was to implement a new method to synthesize cossonidine (also named davisine), a representative diterpenoid alkaloid,” she says. “Synthesis of cossonidine helps us gain insight into the molecule’s structure and the effect that structural and chemical changes have on biological activity. By completing the total synthesis of cossonidine, we were able to use a new strategy — introducing key atoms via a strained intermediate called a benzyne — while also producing a compound that is difficult to isolate so that it, and analogs, can be studied.”
Kisunzu’s second article, “Conformational Properties of a Peptidic Catalyst: Insights from NMR Spectroscopic Studies,” focuses on the research she conducted with the Wennemers research group at the Swiss Federal Institute of Technology (ETH Zurich).
Kisunzu notes that enzymes are nature’s catalysts, making it possible for numerous biochemical reactions to occur rapidly. They consist of long chains of amino acid building blocks, often hundreds of them, which contribute to the overall structure and activity of the enzyme. When a much smaller number of amino acids are connected, the resulting molecules are classified as peptides.
“Peptides have many functions, but can also act as catalysts. Visualizing the structural orientation of peptide catalysts can help us understand their reactivity and selectivity,” she says. “The Wennemers research group developed a highly effective catalyst from three amino acids. The focus of the reported research was to use nuclear magnetic resonance (NMR) spectroscopy, a method that gives us connectivity and distance data, along with computational chemistry methods to model the structure of this catalyst. The resulting picture can help us discern which interactions and properties are important for reactivity.”