Scaled-up production of poacic acid, a plant-derived antifungal agent

A practical three-step synthetic procedure was developed for scale production of poacic acid, a plant-derived fungicide, needed for field trials. This procedure, which relies on simple, straightforward reactions and only one purification step, could be adapted for the production of poacic acid on an industrial scale. [Display omitted] •A three-step synthetic procedure has been developed for producing poacic acid.•Bubbled air was used for removing acetone to improve product yields.•Minor impurities were telescoped into the hydrolysis step to minimize column purifications.•Reduction to only one purification step facilitates future industrial production of poacic acid. Poacic acid, a decarboxylated product from 8–5-diferulic acid that is commonly found in monocot lignocellulosic hydrolysates, has been identified as a natural antifungal agent against economically significant fungi and oomycete plant pathogens. Starting from commercially available or monocot-derivable ferulic acid, a three-step synthetic procedure has been developed for the production of poacic acid needed for field testing in a controlled agricultural setting. First, ferulic acid was esterified to produce ethyl ferulate in 92% yield. Second, peroxidase-catalyzed free radical dehydrodimerization of ethyl ferulate produced crude diferulates, mainly 8–5-diferulate, in 91% yield. Finally, crystalline poacic acid was obtained in 25% yield via alkaline hydrolysis of the crude diferulates after purification by flash-column chromatography. This new procedure offers two key improvements relevant to large-scale production: 1) bubbling air through the reaction mixture in the second step to remove acetone greatly improves the recovery efficiency of the crude diferulates; and 2) telescoping minor impurities directly into the alkaline hydrolysis step eliminates the need for additional column purifications, thus reducing the overall cost of production and removing a major impediment to process scale-up.