The Chemical Cascade That Led Me to Science

Author: Thomas Tao

Photo: Thomas Tao, then-undergraduate Biology and Chemistry student at Skidmore College and now-Organic Catalysis and Chemical Biology PhD student at Columbia University, in a blue lab coat and safety goggles alongside Dr. Aneta Turlik, Visiting Assistant Professor of Chemistry at Skidmore College, in a white lab coat. They are standing in a research laboratory. The photo was captured by Yutian Feng, current student at Skidmore.

Like many other researchers in organic chemistry, I fell in love with science through this fascinating field. I was deeply attracted by the logic of organic synthesis and the art of retrosynthetic planning. Processing organic reactions and designing catalysts are super logical and even magical to me. Thus, as a biology and chemistry undergraduate at Skidmore College, I joined Dr. Aneta Turlik's research group. She was my Organic Chemistry I professor, and one of the best teachers and researchers whom I have ever met.

On the first day of our research group, she presented to us a "magical" cascade reaction leading to the total synthesis of vindoline, one of the most used chemotherapies, developed by Dr. Dale L. Boger's research group at Scripps Research.[1] I was so intrigued by Dr. Turlik's logical presentation of the cascade reaction which goes through three (retro)-cycloaddition processes with a >20:1 diastereoselectivity, while none of the intermediate species were isolated. Dr. Turlik trained me on how to use quantum calculation to elucidate the chemo-selectivity and reaction processes. In addition to acquiring useful skills, I learned critical thinking in theoretical chemistry reactions—how to design calculation experiments to characterize favorable and unfavorable interactions.

In addition to the vindoline projects, Dr. Turlik's interdisciplinary background in density functional theory (DFT) and total synthesis of natural products led to our second project—total synthesis of Myrtaceae terpenoids, where we used DFT to predict reaction selectivity to plan our retrosynthesis. I was very encouraged by the successful progress on this project. The moment that I characterized my first natural product with confidence was nothing but rewarding! These gratifying experiences solidified my decision to apply for a PhD program in my junior year of undergraduate studies, as I was eager to dive deeper into the captivating world of research. I am now a PhD student in chemical biology at Columbia University.

Photo: Thomas Tao presenting his scientific research poster at Skidmore College, spring of 2024.

As an international student working in organic chemistry, I always experience difficulty in remembering the chemist's name on named reactions. However, I benefited from the fact that organic chemistry is a highly logical field with minimal emphasis on memorization. In addition, the inclusive and supportive environment at Skidmore College made the process much easier and encouraging. During my undergraduate research experience, I also benefited from attending various conferences in organic chemistry (e.g., Reaction Mechanisms Conference) and outside of organic chemistry (e.g., American Society for Microbiology Annual Conference).

Eventually, I developed a profound interest in the field of biocatalysis. I am amazed by the incredible chemoselectivity of enzymes or biological catalysts (e.g., catalytic antibodies, nucleotide acids, and other biomimetic catalysts) and their applications in in vivo chemistry/therapeutics and green chemistry. I also believe the engineered enzyme catalysis will achieve the chemistry that can unlock pathways that are impracticable for small-molecule-catalyzed chemistry, providing a viable solution for the total synthesis of natural products.

I hope that you enjoyed reading my personal story!

References:

1. Choi, Y., Ishikawa, H., Velcicky, J., Elliott, G. I., Miller, M. M., & Boger, D. L. (2005). Total Synthesis of (−)-and e nt-(+)-Vindoline. Organic Letters, 7(20), 4539–4542.