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 mu g/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 mu g/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.