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

“A simple screening methodology was employed to correlate the structures of hydroxy-cinnamic 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.”

Phytotoxicity test over Capsicum annum leaves. (I) Negative control a and b: sterile distilled water. (II) Positive control Busan® 30WB a: 71.52 mM and b: 107.28 mM. (III) Isobutyl o-coumarate a: adjuvant control and b: 5 mM isobutyl o-coumarate with adjuvant (in vivo effective dose). (IV) Isobutyl o-coumarate a: adjuvant control and b: 50 mM isobutyl o-coumarate with adjuvant (tenfold the in vivo effective dose). In every test, a 35 μL drop was placed in the leaf.

Highlights:

• “One of the major advantages of the system proposed in this study is the reutilization of the catalyst; the SpinChem® rotating bed reactor allows the recovery of the catalyst for further reaction cycles which enhances the overall productivity of the catalytic strategy.”
• “The excellent conversion yield for the synthesis of iBoC achieved with this strategy allows us to obtain 15 g of product for each reaction cycle with the possibility of catalyst reuse.”
• “Moreover, this strategy can be easily scaled up for the big-scale production of iBoC.”