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

Abstract

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 AÀ 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.

Synthesis of Cyclotetrapeptides Analogues to Natural Products as Herbicides

“…The herbicidal activity of cyclotetrapeptides 16 – 25 , 27 and the linear precursors 4 – 8 , 10 , 12 – 15 were evaluated for their influence on germination, leaf development and radicle length growth of ryegrass seeds at 67 μg/mL using germination in agar methodology [ 32 ]. DMSO was used as negative control and the herbicide S -metolachlor as positive control.…”

“…Our group has recently reported the phytotoxic evaluation of natural products versicotides, among which versicotide D ( 3 , Figure 1 ) shows low cytotoxicity on HepG2 cells [ 31 ], high phytotoxicity (74% radicle growth inhibition at 67 μg/mL) and the ability to inhibit cyanobacteria population with a substantial depletion of the concentration of microcystins in the media [ 32 ]. Here, we report the synthesis of a library of cyclic tetrapeptides inspired on tentoxin and versicotide D and the evaluation of their phytotoxicity against Ryegrass ( Lolium multiflorum ) seeds.…”

Marine natural products

“…263 A convergent synthetic strategy was utilised in the total synthesis of aspergillolide 264 and a biomimetic route was employed in the synthesis of asperoketal A which also provided evidence for the biosynthetic hypothesis proposed. 265 Asymmetric total synthesis of asnovolins A and E utilised anionic fragment coupling to construct the sterically crowded skeleton 266 and solid peptide synthesis was employed to assemble the cyclic pentapeptides, versicotides E and F. 267 Indole diterpenoids (+)-shearinines G and D were prepared via a convergent route. 268 The C-2 reverse prenyltransferase, NotF was characterised and it was then used in the rst synthesis of eurotiumin A, 269 synthesis of (−)-eurothiocin A was achieved in 14 linear steps from commercially available starting materials, 270 the triazole penipanoid A was prepared from 4methoxyphenyl acetic acid 271 and total synthesis of the 13membered macrolide (−)-melearoride A was achieved via a route including a Julia-Kocienski olenation.…”

Synthesis of Cyclopeptides Analogues of Natural Products and Evaluation as Herbicides and Inhibitors of Cyanobacteria

“…The natural cyclopeptide versicotide D isolated from Aspergillus versicolor LZD-14-1 shows low cytotoxicity on HepG2 cells, 15 ability to inhibit cyanobacteria population with a substantial depletion of the concentration of microcystins in the media. 16 Previously, our group reported the phytotoxic evaluation of peptide precursors and cyclotetrapeptides analogues of tentoxin and versicotide D (Table 1). 17 In this work, we present the synthesis of new analogues, with a focus on the influence in the phytotoxic activity given by the change of Gly by β-Ala in the peptide sequence, the increase in ring size by the addition of Ala to obtain cyclopentapeptides, and the change of Leu by Lys.…”

“…tenuis), causes seedling chlorosis. The natural cyclopeptide versicotide D isolated from Aspergillus versicolor LZD-14-1 shows low cytotoxicity on HepG2 cells, high phytotoxicity, and the ability to inhibit cyanobacteria population with a substantial depletion of the concentration of microcystins in the media …”