Scalable total synthesis and comprehensive structure–activity relationship studies of the phytotoxin coronatine

Littleson, Mairi M. and Baker, Christopher M. and Dalencon, Anne J. and Frye, Elizabeth C. and Jamieson, Craig and Kennedy, Alan R. and Ling, Kenneth B. and McLachlan, Matthew M. and Montgomery, Mark G. and Russell, Claire J. and Watson, Allan J. B. (2018) Scalable total synthesis and comprehensive structure–activity relationship studies of the phytotoxin coronatine. Nature Communications. ISSN 2041-1723 (In Press)

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    Abstract

    Natural phytotoxins are valuable starting points for agrochemical design. Acting as a jasmonate agonist, coronatine represents an attractive herbicidal lead with novel mode of action and has been an important synthetic target for agrochemical development. However, both restricted access to quantities of coronatine and, a lack of a suitably scalable and flexible synthetic approach to its constituent natural product components, coronafacic and coronamic acids, has frustrated development of this target. Here, we report gram-scale production of coronafacic acid that allows a comprehensive structure–activity relationship study of this target. Biological assessment of a >120 member library combined with computational studies have revealed the key determinants of potency, rationalising hypotheses held for decades, and allowing future rational design of new herbicidal leads based on this template.