Stereoselective Oxidation of alpha-Copaene, a Fire Ant Repellent Sesquiterpene from Essential Oil of Dipterocarpus Turbinatus

Authors: GINSON, GEORGE - University Of Mississippi; FARHAN, MAHMOOD SHAH - University Of Mississippi; ABBAS, ALI - University Of Mississippi; DILEEP, KUMAR GUDDETI - University Of Mississippi; NOURA, ALOWAFI - University Of Mississippi; LEE, JOSEPH - University Of Mississippi; Chen, Jian; KHAN, IKHLAS - University Of Mississippi; XING, CONG-LI - University Of Mississippi

Submitted to: Journal of Natural Products
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/15/2024
Publication Date: 8/28/2024
Citation: Ginson, G., Farhan, M., Abbas, A., Dileep, K., Noura, A., Lee, J., Chen, J., Khan, I.A., Xing, C. 2024. Stereoselective Oxidation of alpha-Copaene, a Fire Ant Repellent Sesquiterpene from Essential Oil of Dipterocarpus Turbinatus. Journal of Natural Products. https://doi.org/10.1021/acs.jnatprod.4c00758.
DOI: https://doi.org/10.1021/acs.jnatprod.4c00758

Interpretive Summary: Imported fire ants, including the red, black, and hybrid imported fire ants, are significant pest ants. Repellents can be used to prevent foraging fire ants from entering sensitive areas, including electrical equipment, nursing homes, and hospitals. Recent research indicates that repellents can even suppress attacks from agitated fire ants. In this study, a naturally occurring compound, (–)-a-copaene, was found to be a fire ant repellent. Some of its oxidative products exhibit even stronger repellency against fire ants, indicating that fire ant repellents can be enhanced by chemical modification of the initial repellent compounds. This study will contribute to fire ant management by aiding the search for fire ant repellents.

Technical Abstract: Bioassay-guided fractionation of the essential oil extracted from gurjun balsam (Dipterocarpus turbinatus) resulted in the identification of (–)-a-copaene (1) as the repellent constituent with a minimum repellent effective dose (MRED) of 15.6 'g/g against both red imported fire ants (Solenopsis invicta) and hybrid imported fire ants (Solenopsis invicta x Solenopsis richteri). Stereoselective oxidation of 1 via autoxidation and chemical methods produced (–)-a-copaene hydroperoxide (2), (+)-copa-4-en-3ß-ol (3), (–)-a-copaene oxide (4), (+)-ß-copaen-4 ß -ol (5), (+)-copaenediol (6), and (+)-copaene ketol (7). The stereochemistry of the six compounds was unequivocally established by detailed analysis of 2D NMR spectroscopic data, clarifying confusions for the stereochemical assignments of compounds 3–7 in the literature. Compounds 2–7 showed repellency with MREDs ranging from 3.9–15.6 ug/g against hybrid and red im-ported fire ants. Molecular docking was utilized to probe the binding of compounds 1–7 to the hybrid imported fire ant pheromone-binding protein GP-9, providing structural insights into the repellency of these compounds.