Screening, synthesis optimization, and scaling-up of phytopathogen antifungals derived from natural hydroxycinnamic acids.

ABSTRACT

A simple screening methodology was employed to correlate the structures of hydroxycinnamic acids (HCAs) and their esterified derivatives with their in vitro antifungal activity over Fusarium oxysporum f. sp. lycopersici. The antifungal activity of the tested HCAs, i.e., coumaric > ferulic > sinapinic > caffeic acid, was higher after esterification and when the coumaric acid hydroxyl group was at the ortho-position. This outcome was strengthened by the elongation of the alkyl chain to 4-carbons and, particularly, by the esterification with isobutyl alcohol. The highest antifungal activity was obtained from isobutyl o-coumarate (iBoC), which inhibits 70% of mycelial growth at 1.2 mM. Thereby, a heterogeneous catalysis strategy was optimized by using the response surface methodology. At the best conditions found, the synthesis of iBoC was scaled up to 15 g, achieving 96% conversion yield in 48 h in a stirred batch reactor. This study reveals for the first time the potential of iBoC to provide commercial materials as antifungal agents to control F. oxysporum and other phytopathogenic fungi. Supplementary Information The online version contains supplementary material available at 10.1007/s13205-022-03425-7.