Cyclopeptides Natural Products as Herbicides and Inhibitors of Cyanobacteria: Synthesis of Versicotides E and F

The first total synthesis of cyclopeptides versicotide E and F, natural products produced by marine fungus Aspergillus versicolor LZD‐14‐1, was achieved in good yield by solid phase peptide synthesis (SPPS) of their linear precursors and solution phase cyclization. All the versicotides A−F were evaluated as herbicides and inhibitors of cyanobacterial growth. Versicotides A, B, D, E and F showed a significant inhibition of Rye grass seed's radicle growth at a concentration of 67 μg/mL. Versicotides A, B and D also inhibited seed germination and leaf development. On the other hand, Versicotides D and F caused a relevant reduction on Microcystis aeruginosa population when cultures on exponential growth were incubated with 40 μg/mL solutions of these compounds. Evaluation of the concentration of microcystins after these treatments showed that versicotide D inhibited the production of microcystins in a comparable extent to the positive control, colistine. These results indicate versicotides, with versicotides D and F as top hits, could be considered as lead candidates in the development of bioherbicides able to mitigate the environmental impact that the evolution of agriculture has had on water quality. The first total syntheses of cyclopeptides versicotide E and F, containing anthranilic acid, are reported. Evaluation of the herbicide activity, cyanobacteria inhibition and microcystins concentration of all versicotides A−F demonstrated that several of them could be considered as lead candidates in the development of bioherbicides to mitigate the environmental impact that the evolution of agriculture has had on water quality.