Total synthesis and structure-activity-relationship of Alternaric acid delivers an herbicide vector

Eva M. Israel; Júlia Comas-Barceló; Alexandra M. Z. Slawin; Allan J. B. Watson

doi:10.1038/s44160-022-00169-3

Total synthesis and structure-activity-relationship of Alternaric acid delivers an herbicide vector

Eva M. Israel, Júlia Comas-Barceló, Alexandra M. Z. Slawin, Allan J. B. Watson

Research output: Contribution to journal › Article › peer-review

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Abstract

Global food security is one of the foremost challenges of our time and requires a multifaceted solution. Crop protection strategies are an essential part of this response; however, there is increasing resistance to known modes of action. Since its discovery in 1949, the natural product alternaric acid has been proposed as a starting point for herbicide development. However, this target is undeveloped due to its poor synthetic accessibility and a lack of knowledge of the associated pharmacology. Here we report the discovery of herbicidal compounds from alternaric acid that operate via a potentially unknown mode of action. Development of a total synthesis enabled structure–activity relationship profiling of compound libraries, which, combined with phenotypic screening and molecular modelling data, identified small-molecule lead compounds with enhanced and broader spectrum herbicidal activity than alternaric acid.

Original language	English
Journal	Nature Synthesis
Volume	First Online
Early online date	13 Oct 2022
DOIs	https://doi.org/10.1038/s44160-022-00169-3
Publication status	E-pub ahead of print - 13 Oct 2022

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10.1038/s44160-022-00169-3

Manuscript AAM
Copyright © 2022, The Author(s), under exclusive licence to Springer Nature Limited . For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) public copyright Licence to any Accepted Author Manuscript version arising. The final published version of this work is available at https://doi.org/10.1038/s44160-022-00169-3
Accepted author manuscript, 4.74 MBLicence: CC BY

Scalable total synthesis and SAR delivers a new agrochemical herbicidal lead from Alternaric Acid (dataset)
Watson, A. J. B. (Creator), Israel, E. M. (Creator), Comas-Barcelo, J. (Creator) & Slawin, A. M. Z. (Creator), University of St Andrews, 9 Nov 2022
DOI: 10.17630/c41bcf9c-57cc-46f2-94cf-c9f7559554c5
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AU - Watson, Allan J. B.

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Total synthesis and structure-activity-relationship of Alternaric acid delivers an herbicide vector

Abstract

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Scalable total synthesis and SAR delivers a new agrochemical herbicidal lead from Alternaric Acid (dataset)

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