Determination of the Absolute Configuration and Phytotoxicity of Mevalocidin Enantiomers

Authors: V.A.R ANNAM, SURESH CHANDRA - University Of Mississippi; PANDEY, PANKAJ - University Of Mississippi; Bajsa Hirschel, Joanna; DUKE, STEPHEN - University Of Mississippi; CHITTIBOYINA, AMAR - University Of Mississippi

Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/30/2026
Publication Date: 7/11/2026
Citation: V.A.R Annam, S., Pandey, P., Bajsa Hirschel, J.N., Duke, S.0., Chittiboyina, A. 2026. Determination of the Absolute Configuration and Phytotoxicity of Mevalocidin Enantiomers. Journal of Agricultural and Food Chemistry. https://doi.org/10.1021/acs.jafc.6c04623.
DOI: https://doi.org/10.1021/acs.jafc.6c04623

Interpretive Summary: The study uncovers the absolute stereochemistry of mevalocidin—a fungal-derived hydroxy acid with potent herbicidal activity—by carrying out a fully stereocontrolled total synthesis. Beyond revealing the active natural enantiomer, the scalable synthetic route offers a flexible foundation for developing new chiral herbicidal molecules. Together, these insights highlight the promise of mevalocidin and its analogs as sustainable, biologically derived tools for agriculture, especially within organic farming systems.

Technical Abstract: The absolute stereostructure of mevalocidin, a fungal-derived hydroxy acid bioherbicide featuring a critical tertiary carbinol stereocenter, was elucidated through a stereocontrolled total synthesis. The key transformation employed an Evans condensation between a (+)-N-acetyl-4-benzyl-2-oxazolidinone chiral auxiliary and a prefunctionalized ketone electrophile. The resulting approach yielded two separable diastereomeric adducts, which were transformed into both enantiomers of mevalocidin. Phytotoxicity assays againstLemna paucicostata(duckweed) identified (+)-mevalocidin with a 3S-configuration at the stereogenic center, as the biologically active isomer, exhibiting an IC50 of 120 ± 24 nM after 10 days of single treatment. Notably, the corresponding lactone possessing the 3S configuration also induced significant growth inhibition, whereas the 3R-isomer of the hydroxy acid or lactone forms exhibited negligible effects on frond development. The pronounced biologically active enantiomer and its sub-micromolar phytotoxicity underscore its potential for sustainable agricultural applications, particularly in organic farming. Furthermore, this scalable synthetic route provides a versatile platform for the development of structurally related chiral herbicidal agents with optimized phytotoxicity and selectivity.