Leaps-MPS: innovative platform to access hexocannabitriol and analogs for biological & antioxidant evaluation

The National Science Foundation's Division of Chemistry is funding a two-year research project at the University of Michigan-Flint through the Mathematical and Physical Sciences program (CFDA 47.049) under the Launching Early-Career Academic Pathways (LEAPS-MPS) initiative. Awarded on September 1, 2025, for $250,000, Professor Camelio's research team will develop innovative synthetic chemistry strategies to synthesize hexocannabitriol, a newly isolated natural product, and create a modular library of structural analogs. The project will employ a one-pot synthesis protocol designed to efficiently install multiple functional groups simultaneously, enabling rapid generation of related compounds for subsequent evaluation.

The synthesized hexocannabitriol and analog compounds will undergo comprehensive biological and antioxidant assessments through interdepartmental collaborations. Specifically, the research team will evaluate the compounds' capacity to induce the Nuclear factor erythroid 2-related factor 2 (NRF2) pathway, their efficacy as potential antioxidants, and their potential applications as antimicrobial agents. The project will conclude by August 31, 2027, and incorporates significant educational components, providing undergraduate students with training in synthetic organic chemistry and exposure to interdisciplinary research methodologies across multiple chemistry subdisciplines.

Abstract

In this project, funded by the MPS-leaps (launching early-career academic pathways) program and managed by the division of chemistry (CHE), professor camelio and her students at the university of michigan-flint will perform studies focused on the development of a chemical synthesis strategy to access a newly isolated natural product, hexocannabitriol. To address gaps in fundamental knowledge regarding the activity of this newly isolated, biologically relevant natural compound, professor camelio and her students will synthesize hexocannabitriol and analogs with varying structural differences. The synthesized natural product and corresponding analogs will then be evaluated for biological activity through interdepartmental collaborations. This will expand the current understanding of hexocannabitriol and analogs potentially uncover novel modes of activity. In addition, undergraduate students will be trained in synthetic organic chemistry and biological studies providing students the opportunity to participate in a collaborative interdepartmental research program covering different areas of chemistry. Professor camelio and her students will synthesize hexocannabitriol and related analogs in a modular approach. This project will investigate a one-pot protocol to install multiple critical functional groups within a single operation, and enables the potential to rapidly synthesize a library of molecules related to hexocannabitriol. Ultimately, the natural product, hexocannabitriol, and relevant analogs will be evaluated to 1) determine the ability to induce the NRF2 pathway; 2) determine the efficacy as potential antioxidants; and 3) evaluate the potential for use as antimicrobial agents. This project involves interdepartmental collaborations to further the understanding on a new class of natural compounds, and to generate key fundamental knowledge. The research into this new natural product, and its novel synthetic analogs, could have broader impact in development of innovative bioactive compounds. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the foundation's intellectual merit and broader impacts review criteria.- subawards are not planned for this award.