Synthesis and biological profile of substituted hexahydrofuro[3,4‐b]furans, a novel class of bicyclic acyl‐acyl carrier protein (ACP) thioesterase inhibitors

Author:

Ahrens Hartmut1,Barber David M.1ORCID,Bojack Guido1,Bollenbach‐Wahl Birgit1,Churchman Luke1,Getachew Rahel1,Helmke Hendrik1,Hohmann Sabine1,Laber Bernd1,Lange Gudrun1,Rees Shaun1,Reingruber Anna M.1,Schmutzler Dirk1,Frackenpohl Jens1ORCID

Affiliation:

1. Research and Development, Weed Control, Division Crop Science Bayer AG, Industriepark Höchst Frankfurt am Main Germany

Abstract

AbstractBACKGROUNDWeed control is a significant challenge for farmers around the globe. Of the various methods available for combatting weeds, small molecules remain the most effective and versatile technology to date. In the search for novel chemical entities with new modes of action toward herbicide‐resistant weeds, we have investigated hexahydrofuro[3,4‐b]furan‐based acyl‐acyl carrier protein (ACP) thioesterase inhibitors inspired by X‐ray co‐crystal structure‐based modeling studies.RESULTSBy exploiting scaffold hopping concepts and molecular modeling studies we were able to identify new hexahydrofuro[3,4‐b]furan‐based lead structures showing promising activity in vivo against commercially important grass weeds in line with strong target affinity.CONCLUSIONThe present work covers a series of novel herbicidal lead structures that possess a hexahydrofuro[3,4‐b]furan scaffold as a structural key feature, carrying ortho‐substituted aryloxy side chains. Based on an optimized synthetic approach a broad structure–activity relationship (SAR) study was carried out. The new compounds emerging from our modeling‐inspired structural variations show good acyl‐ACP thioesterase inhibition in line with promising initial herbicidal activity. Glasshouse trials showed that the hexahydrofuro[3,4‐b]furans outlined herein display good control of cold and warm season grass‐weed species in pre‐emergence application. Remarkably, some of the novel acyl‐ACP thioesterase‐inhibitors also showed promising efficacy against warm season weeds that are difficult to control. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Publisher

Wiley

Reference36 articles.

1. Cinmethylin controls multiple herbicide‐resistant Lolium rigidum and its wheat selectivity is P450‐based

2. United Nations PopulationAvailable:https://www.un.org/en/global-issues/population[7 February 2024].

3. Current status and future prospects in herbicide discovery;Dayan FE;Plan Theory,2019

4. A Competitive Edge: Competitor Inspired Scaffold Hopping in Herbicide Lead Optimization

5. Inspired by Nature: Isostere Concepts in Plant Hormone Chemistry

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