A New Class of Diaryl Ether Herbicides: Structure-Activity Relationship Studies Enabled by a Rapid Scaffold Hopping Approach.

Autor: Kalnmals CA; Discovery Chemistry, Small Molecule Discovery and Development, Corteva Agriscience, Indianapolis, Indiana 46268, United States., Benko ZL; Discovery Chemistry, Small Molecule Discovery and Development, Corteva Agriscience, Indianapolis, Indiana 46268, United States., Hamza A; Discovery Chemistry, Small Molecule Discovery and Development, Corteva Agriscience, Indianapolis, Indiana 46268, United States., Bravo-Altamirano K; Discovery Chemistry, Small Molecule Discovery and Development, Corteva Agriscience, Indianapolis, Indiana 46268, United States., Siddall TL; Discovery Chemistry, Small Molecule Discovery and Development, Corteva Agriscience, Indianapolis, Indiana 46268, United States., Zielinski M; Mode of Action and Resistance Management Center of Expertise, Integrated Biology and Field Sciences, Corteva Agriscience, Indianapolis, Indiana 46268, United States., Takano HK; Mode of Action and Resistance Management Center of Expertise, Integrated Biology and Field Sciences, Corteva Agriscience, Indianapolis, Indiana 46268, United States., Riar DS; Herbicide Biology, Integrated Biology and Field Sciences, Corteva Agriscience, Indianapolis, Indiana 46268, United States., Satchivi NM; Herbicide Biology, Integrated Biology and Field Sciences, Corteva Agriscience, Indianapolis, Indiana 46268, United States., Roth JJ; Discovery Chemistry, Small Molecule Discovery and Development, Corteva Agriscience, Indianapolis, Indiana 46268, United States., Church JB; Herbicide Biology, Integrated Biology and Field Sciences, Corteva Agriscience, Indianapolis, Indiana 46268, United States.
Jazyk: angličtina
Zdroj: Journal of agricultural and food chemistry [J Agric Food Chem] 2023 Nov 29; Vol. 71 (47), pp. 18171-18187. Date of Electronic Publication: 2023 Jun 23.
DOI: 10.1021/acs.jafc.3c01285
Abstrakt: We report on the development of a novel class of diaryl ether herbicides. After the discovery of a phenoxybenzoic acid with modest herbicidal activity, optimization led to several molecules with improved control of broadleaf and grass weeds. To facilitate this process, we first employed a three-step combinatorial approach, then pivoted to a one-step Ullmann-type coupling that provided faster access to new analogs. After determining that the primary target site of our benchmark diaryl ethers was acetolactate synthase (ALS), we further leveraged this copper-catalyzed methodology to conduct a scaffold hopping campaign in the hope of uncovering an additional mode of action with fewer documented cases of resistance. Our comprehensive and systematic investigation revealed that while the herbicidal activity of this area seems to be exclusively linked to ALS inhibition, our molecules represent a structurally distinct class of Group 2 herbicides. The structure-activity relationships that led us to this conclusion are described herein.
Databáze: MEDLINE
Externí odkaz: