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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - EXPHYLL (Discovery of new herbicides through an exploration of the chemistry and biology of the naturally occurring phyllostictines)

Teaser

Summary

\"With a rapidly growing world population combined with a loss of available agricultural land, there is an urgent need to increase the efficiency of food production to prevent global food shortages. Herbicides play an important part in improving crop yields by protecting them from invasive weeds. To address the rising levels of resistance emerging against existing crop protection agents, and to improve the environment safety associated with such agents, there is an urgent need to discover and develop new herbicides with novel mechanisms of action to fight weeds. In this search, natural products with their unique chemical architectures and prominent bioactivities offer an excellent entry point. In 2008, researchers discovered a new and promising class of herbicide produced by a common fungus. The most active compound was named phyllostictine A and was shown be more active in an assay against the wheat pest thistle than fusaric acid, a well-known and powerful toxin; and faster acting than the well known and often used herbicide glyphosate. Consequently, phyllostictine A offers a potentially exciting new lead in the development of new herbicides.

The overall objectives of the project were to:

- develop new sustainable chemical methods that can be used to make phyllostictine A and related chemical structures in the laboratory;

- make the natural product in the laboratory, to unambiguously confirm its chemical structure and determine the \"\"handedness\"\" (chirality) of the molecule.

- explore the weed killing potential of the new chemicals made under this programme to see if we can find new, easy-to-make compounds that mimic the behaviour of the natural product.

- use these new agents to help learn how phyllostictine kills weeds at the molecular level.\"

Work performed

During this fellowship, Dr Martin Riemer successfully completed the first chemical synthesis of phyllostictine A at the University of Warwick, UK and helped resolve the structural ambiguities surrounding this natural product. This was accomplished in 15 chemical steps using a range of innovative chemical transformations. The subunit of the natural product responsible for plant growth inhibition was also identified, paving the way for the potential development of more readily accessible derivatives active as herbicides. Specifically, simple 3-methylene tetramic acids were produced that displayed effect plant growth inhibitory activity against weeds. Thus, the part of the natural product responsible for the biological activity has been successfully identified. The initial elements of this work were published in open-access journal in 2018 with Dr Riemer as first author. The work has been further disseminated at several scientific meetings.

Final results

These finding pave the way for the development of simple 3-methylene tetramic acids as potential new types of herbicide. The biological activities obtained are comparable to, and in some cases even better than, the activity of the very well-known herbicide glyphosate. Hence, these structures can be regarded as an interesting starting point for the development of potential crop protection products based on natural products. Work is ongoing to further develop and refine the properties of this class of agent.