Exploitation of the century-old Zincke ring-opening reaction of pyridines for the development of new methods for natural product synthesis is the focus of the research supported by this grant. Specifically, the proposed research involves the further development of methods for converting pyridines into other heterocycles and for generating stereodefined dienes and polycyclic lactams from the pyridine-ring-opened products, called Zincke aldehydes. Each of these reaction types is applicable to problems in natural product synthesis.
With this CAREER award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Christopher Vanderwal of the Department of Chemistry at the University of California, Irvine. Professor Vanderwal's research focuses on natural product synthesis and new reaction discovery for applications in the pharmaceutical field. Professor Vanderwal is also seeking to improve informal and formal communication skills for graduate students in chemistry. Key aspects of this program include the introduction of a graduate student hosted seminar series and graduate-level seminar courses, wherein the students present the lecture materials to each other.
The work supported by this CAREER grant served to advance the field of chemical synthesis, provided exceptional training to multiple undergraduate and graduate students, facilitated interactions of UCI graduate students with eminent scientists, and permitted access to scientific experiments for underprivileged local middle school students. The intellectual merit of the work is largely related to improved access to complex organic molecules from simple, commodity chemicals. For example, we demonstrated that pyridines, very inexpensive feedstock chemicals, can be easily converted into high-value-added compounds that might be useful in drug discovery. The fascinating chemical process that converts these simple starting materials into complex molecules was also studied with the aid of computational chemistry, which helped us understand the way these transformations work. That new insight should permit extrapolation of this chemistry to other systems, making the impact of our work more broad. The crowning achievement of this work, from a purely academic standpoint, was a very short chemical synthesis of the well-known toxic alkaloid strychnine. The subject of nearly 20 previous syntheses by other research groups, the most direct previous synthesis comprised a route of a dozen linear chemical steps; ours proceeds in exactly half that many. With this achievement, we demonstrated clearly that complex molecules, such as the classic benchmark molecule strychnine, can be made in very short order from pyridines, which are among the cheapest and most widely available commercial chemicals. The most important broader impact of the research portion of this grant is certainly the training of the next generation of organic chemists. The research activity of five doctoral students (three have obtained their PhDs at the time of writing), two MS students, and multiple undergraduates were partially or completely funded by this grant. Our doctoral graduates have gone on to excellent postdoctoral or industrial positions, with one recently accepting a faculty position in chemistry. The two masters graduates have gone on to excellent positions in the chemical industry, and all undergraduates began graduate school in chemistry at excellent institutions. Outside of the direct benefits to our research group, this grant permitted many organic chemistry graduate students at UCI to interact closely with multiple world-renowned chemists through our Student-Hosted Seminar Series that I implemented. Each year, two or three famous academic chemists visited our department as part of this program, and during each visit they interacted with approximately 20 different graduate students in the course of research meetings and meals. This program continues, funded by multiple sources, long after completion of this grant. Finally, local middle school students from institutions with little scientific infrastructure were invited quarterly to UCI for the LEAPS (Laboratory Experiments and Activities in the Physical Sciences) program. Our research group co-hosted these events, with typically 10–15 students, mostly underrepresented minorities, coming to our labs to learn some basic chemistry in the context of fun and visually appealing, hands-on experiments. This program is also ongoing.
