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 against Lemna paucicostata (duckweed) identified (+)-mevalocidin with a 3 S -configuration at the stereogenic center, as the biologically active isomer, exhibiting an IC 50 of 120 ± 24 nM after 10 days of single treatment. Notably, the corresponding lactone possessing the 3 S configuration also induced significant growth inhibition, whereas the 3 R -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.