Blake Catlett | November 2, 2022

Dr. Schuppe is also the head of the Schuppe lab. The group is focused on improving the synthetic process of useful and important biological molecules. They also look to discover new combinations of reactions that are catalyzed by metallic ions that free up space within the product materials.

Dr. Schuppe began his education at the University of Texas at Austin. Early on in his time at the university, he joined an organic chemistry lab as an undergraduate researcher. The lab worked on synthesizing and testing the abilities of neurologically active molecules. His experience in the lab inspired him to pursue a career in research, and continued onto a Ph.D. at Yale University. There, he worked on improving the synthesis of molecules similar to those he had worked with at UTA. Afterwards, he continued to the Massachusetts Institute of Technology, where he started working on tools and methods to further improve such molecular synthesis.

Dr. Schuppe was drawn to Vanderbilt because of the university’s focus on supporting young researchers and tackling the toughest scientific problems. Dr. Schuppe heavily appreciates Vanderbilt’s commitment to undergraduate and faculty academic success. Collaboration between various Vanderbilt departments was another large selling point for him. In Dr. Schuppe’s research, he is working to synthesize biological molecules, but his lab was not equipped to test all of these molecules’ functions. The university’s connection with Vanderbilt University Medical Center helped resolve this problem. Dr. Schuppe now has access to facilities like the High Throughput Screening (HTS) facility, which allows for the quick synthesis and testing of various molecules.

Over the course of his professional career, Dr. Schuppe’s main focus has been on the synthesis of and development of better synthesis methods for biological molecules. Currently, the Schuppe Lab is interested in taking existing natural molecules and figuring out how to synthesize or edit them rapidly to produce them en masse. Moreover, they’re looking for ways to maximize these molecules’ specific properties and investigate the application of these properties to real world problems. One specific method that the Schuppe Lab is working on is asymmetrical catalysis. When working with large biological molecules, various enantiomers and stereoisomers, or molecules with the same chemical formula but different shapes, are typically present. These different shape can cause molecules to — instead of carrying out its normal function —  have an undesired effect or no effect at all. To tackle this issue, the lab is working on the design of protocols for certain pharmaceutical molecules that will ensure that only the desired conformation is produced during synthesis. These protocols would allow for accurate mass production of molecules for drug research and development in the future.

    One molecule which has been a focus of Dr. Schuppe’s research is xylogranatopyridine B, a molecule of interest because of the way it was originally believed to inhibit the PTB1B protein. The synthesis of this inhibitor molecule was first presented in a paper published on ChemRxiv in 2022, for which Dr. Schuppe was an author. Dr. Schuppe’s group was interested in the inhibition of the PTB1B protein for applications in medical research, such as the potential prevention of diabetes and neurological diseases.

    The initial hope for the research was to find a way to quickly synthesize xylogranatopyride-B. However, recent reports showed that inhibition of PTB1B protein achieved only moderate success for its intended purposes. The Schuppe group therefore switched gears and searched for different applications for the inhibitor. Eventually, they found novel targets and molecular activities for xylogranatopyridine-B, such as potential anti-inflammatory effects. At the end of the study, along with the newfound activities, the group was able to develop a shortened and simplified eleven-step synthesis for the molecule. The improved synthesis of this molecule allows for further research into the specific medical properties that the molecule has to offer. Further analysis of the activities of xylogranatopyridine-B are needed, however, before the molecule can become a more prominent candidate in drug development. This is just a sample of what we will see coming from the Schuppe lab soon. The research they are doing holds great promise in making an impact in the medical field.

Dr. Schuppe has short and long term goals for his research. In the short term, he is working to identify and investigate the uses of as many proper molecular targets in his synthesis as possible. His long-term vision, however, is simply for his lab to contribute to the advancement of science. He says that his lab “may not be the one to create the new best drug,” but is there to “pose the question of which molecules can be extremely useful and can be used in the next revolutionary compound.”

Dr. Schuppe is passionate about continuing to teach and mentor undergraduate students. He sees it as one of the top benefits of being a professor. For this particular reason, Dr. Schuppe will be accepting students for the Spring 2023 semester. Interested students can contact him via email at alexander.w.schuppe@vanderbilt.edu.

Citations:

Alex Schuppe. Department of Chemistry. https://www.vanderbilt.edu/chemistry/schuppe.php 

Graduate Course Listing. Department of Chemistry. https://www.vanderbilt.edu/chemistry/grad-courses.php 

Home. Schuppe Lab. https://www.schuppelab.com 

Liu Y, Schuppe AW, Zhao Y, Lee J, Newhouse TR. Synthesis of (–)-melazolide B, a degraded limonoid, from a natural terpene precursor. Tetrahedron Chem. 2022. 1:100011. https://www.sciencedirect.com/science/article/pii/S2666951X22000079. doi:10.1016/j.tchem.2022.100011  

Newhouse T, Schuppe A, Liu Y, Zhao Y, Ibarran S, Huang D, Wang E, Lee J, Loria P. Strategies for the De Novo Synthesis of Highly Substituted Pyridine Scaffolds: Unified Total Synthesis of the Limonoid Alkaloids. 2021 Oct 15. https://chemrxiv.org/engage/chemrxiv/article-details/61672f237d3da5f081f6da9c. doi:10.26434/chemrxiv-2021-47tvk

Schuppe AW, Huang D, Chen Y, Newhouse TR. Total Synthesis of (−)-Xylogranatopyridine B via a Palladium-Catalyzed Oxidative Stannylation of Enones. Journal of the American Chemical Society. 2018; 140(6):2062–2066. https://pubs.acs.org/doi/10.1021/jacs.7b13189. doi:10.1021/jacs.7b13189