Determination of the Absolute Configuration and Phytotoxicity of Mevalocidin Enantiomers

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.