Search

BACKGROUND: Whilst there are several methods to control weeds, which continuously plague farmers around the globe, the application of small molecular compounds is still the most effective technology to date. Plants can evolve to become resistant to PPO‐inhibitors, a class of herbicides in commercial use since the 1960s. It is therefore essential to continuously develop new herbicides based on this mode‐of‐action with enhanced intrinsic activity, an improved resistance profile and favourable physicochemical properties. Based on an Amaranthus PPO crystal structure and subsequent modelling studies, halogen‐substituted pyrazoles have been investigated as isosteres of uracil‐based PPO‐inhibitors. RESULTS: By combining structural features from the commercial PPO‐inhibitors tiafenacil and pyraflufen‐ethyl and by investigating receptor‐binding properties, we identified new promising pyrazole‐based lead structures showing strong activity in vitro and in vivo against economically important weeds of the Amaranthus genus: A. retroflexus, and resistant A. palmeri and A. tuberculatus. CONCLUSION: The present work covers a series of novel PPO‐inhibiting compounds that contain a pyrazole ring and a substituted thioacetic acid sidechain attached to the core phenyl group. These compounds show good receptor fit in line with excellent herbicidal activity against weeds that plague corn and rice crops with low application rates. This, in combination with promising selectivity in corn, have the potential to mitigate and affect weeds that have become resistant to some of the current market standards. Remarkably, some of the novel PPO‐inhibitors outlined herein show efficacies against economically important weeds that were superior to recently commercialized and structurally related tiafenacil. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

New 2,3‐dihydro‐1‐benzofuran‐4‐carboxylic acid derivatives have been identified as potent lead structures against drought and cold stress in crops starting from the synthetic exploration of stabilized analogs of the natural product lunularic acid. An optimized Lewis‐acid mediated cyclization gave a short and efficient access to the envisaged 2,3‐dihydro‐1‐benzofuran‐4‐carboxylates. Enantioselective approaches were investigated to assess the potential impact of the chiral center on in vivo activity. Whilst 2,3‐dihydro‐1‐benzofuran‐4‐carboxamides and 2,3‐dihydro‐1‐benzofuran‐4‐carboxylates carrying phenyl substituents with electron‐withdrawing groups exhibited only low to moderate in vivo activity, the corresponding 2,3‐dihydro‐1‐benzofuran‐4‐carboxylates carrying optimized electron‐donating substituents in the phenyl moiety revealed strong in vivo activity, both against drought stress in several broad‐acre crops, as well as against cold stress in corn. Remarkably, several 2,3‐dihydro‐1‐benzofuran‐4‐carboxylates showed stronger efficacy than the internal standards used in our in vivo SAR study. [ABSTRACT FROM AUTHOR]

New oxotetrahydroquinolinyl‐ and oxindolinyl sulfonamides interacting with RCAR/(PYR/PYL) receptor proteins were identified as lead structures against drought stress in crops starting from protein docking studies of a sulfonamide lead structure, followed by in‐depth SAR studies. Optimized five to six step synthetic approaches via substituted amino oxo‐tetrahydro‐quinolines and amino oxo‐indolines as essential intermediates gave access to the envisaged oxo‐tetrahydroquinolinyl and oxindolinyl sulfonamides. Whilst oxo‐tetrahydroquinolinyl sulfonamides with additional carbon substituents or spiro‐cycloalkyl groups exhibited only low to moderate target affinities, the corresponding spiro‐oxindolinyl and oxo‐tetrahydroquinolinyl sulfonamides carrying optimized N‐substituents revealed strong interactions with RCAR/(PYR/PYL) receptor proteins in Arabidopsis thaliana. Remarkably, the in vitro activity observed for these new compounds was on the same level as observed for the naturally occurring plant hormone in line with strong efficacy against drought stress in‐vivo (canola and wheat as broad‐acre crops). [ABSTRACT FROM AUTHOR]

Novel analogues of the plant hormone abscisic acid (ABA) were designed and prepared to explore the impact that modifications of its terpenoid side chain have on receptor affinity and in vivo efficacy against drought stress in selected crops. Their efficient and versatile synthesis proceeded via Stille or Sonogashira couplings, shortening the synthetic route significantly. In line with molecular modelling and X-ray crystallography studies novel ABA-derivatives with small alkyl, cycloalkyl or haloalkyl substituents showed strong effects in vitro and in vivo against drought stress in crops, particularly canola and wheat. [ABSTRACT FROM AUTHOR]

Synthetic analogues of plant hormone abscisic acid (ABA) bearing a yet unexplored head group motif were prepared based on a combination of agrochemical experience, in vivo hits and structure-based design. It could thus be explored how modifying key parts of ABA's cyclohexenone unit influenced receptor affinity and in vivo efficacy against drought stress in selected crops. Cyano-cyclopropyl groups proved to be suitable replacements of the cyclohexanone moiety leading to ABA analogues with strong activity in vitro and in vivo. Their efficient and versatile synthesis proceeded via Stille or Sonogashira couplings as the key steps. Combining novel cyano-cyclopropyl headgroups with previously identified substituents in the terpenoid side chain afforded the most promising effects against drought stress in crops, particularly canola and wheat. [ABSTRACT FROM AUTHOR]

Phytochemistry, Plant stress, Dihydrobenzofurans, Salicylates, Lunularic acid Keywords: Phytochemistry; Plant stress; Dihydrobenzofurans; Salicylates; Lunularic acid EN Phytochemistry Plant stress Dihydrobenzofurans Salicylates Lunularic acid 1 1 1 04/14/22 20220412 NES 220412 B The Front Cover b shows one set of crop species thriving in comparison to the other - despite both enduring cold and drought conditions - as it has been treated with new compounds developed by Frackenpohl and colleagues. Notes on the Lewis acid-mediated cyclization used to synthesize these have been left on the pot of hydrangea flowers, the roots of which contain hydrangeic acid and the plant hormone lunularic acid, which inspired this work. [Extracted from the article]