ASDRP Colloquia January 10, 2023 Benchtop NMR Enabled Studies

"Benchtop NMR Enabled Synthetic Studies of Natural Products and Small Molecule Inhibitors Towards Novel Antiproliferative and Antiviral Agents"

The first project that Sarah worked on was on berberine, a bioactive isoquinoline alkaloid small molecule isolated from a plant whose therapeutic use in treating human disease dates back several centuries in ancient southeast Asia. A few years ago, we and others reported could act as a photosensitizer to excite ground state triplet oxygen into excited state triplet oxygen, thereby acting as photosensitizer for light-induced biological activity, and Sarah has published on this extensively [Photochemical analog (Sun, et al. JEI 2021); Initial antibacterial SAR (Sun, et al. JEI 2020)]. Specifically, Sarah led our first efforts on non-canonical uses of benchtop NMR spectroscopy to use benchtop NMR to quantify 1O2 by trapping it with a cyclic 1,3-diene to form [2.2.2]bicyclo endoperoxides, and we now have two publications on this, along with an application note co-developed with Nanalysis [App Note, Interview Video]. In parallel, Sarah has also grown a great deal of expertise in using computer modeling for understanding reactive intermediates and small molecule drug candidates (Link to Sarah's Ted Talk here), first in our use of DFT, TD-DFT, and MD in our computational SAR of berberine analogs as DNA-Gquad stabilizing agents (Sun/Ashok, et. al., JEI 2020), later in our SARS-CoV-2 Mpro inhibitors project (Sun, et al., J. Res. HS 2020). When we transitioned the project to work on carmofur, a small molecule originally developed for colorectal cancer but later repurposed for SARS-CoV-2, Sarah was involved in a high throughput analog screen of novel carmofur analogs against wild type and mutant variants of SARS-CoV-2 (Luk, et al., manuscript accepted, 2022). Late in 2022, Sarah was part of a team that worked on our group’s flagship paper of the year, using 19F NMR spectroscopy for monitoring (Chen, et al. ChemRXiv 2022), specifically for tracking the reactive intermediates present in complex multicomponent reactions. This project was shared at STEM Week at Los Altos High School (Link to talk:    • Sarah Su on NMR insight into Biginell...  ) and is now under peer review for publication! Currently, Sarah works on several projects in the interface of chemical synthesis, chemical biology, catalysis, and small molecule drug discovery, including our development of difluorocyclopropanation catalyst strategies as well as using stereo- and regio-controlled inverse demand Diels Alder cycloadditions for construction of the tricyclic core of forskolin, a bioactive diterpenoid with therapeutic value in aging research.

Researchers:
Sarah Su, Los Altos High School '23

Advisor: Edward Njoo