Investigations into Simplified Analogues of the Herbicidal Natural Product (+)‐Cornexistin

We report the design, synthesis and biological evaluation of simplified analogues of the herbicidal natural product (+)‐cornexistin. Guided by an X‐Ray co‐crystal structure of cornexistin bound to transketolase from Zea mays, we attempted to identify the key interactions that are necessary for cornexistin to maintain its herbicidal profile. This resulted in the preparation of three novel analogues investigating the importance of substituents that are located on the nine‐membered ring of cornexistin. One analogue maintained a good level of biological activity and could provide researchers insights in how to further optimize the structure of cornexistin for commercialization in the future. (+)‐Cornexistin has long been of interest to the crop protection community due to its interesting herbicidal profile and unique mode of action. However, the complex chemical structure of cornexistin has hindered further research into new analogues. Guided by an X‐Ray co‐crystal structure, we investigated simplified analogues of cornexistin that focused on the effects that the functional groups located on the right‐hand side of the 9‐membered ring have on herbicidal efficacy and target affinity.