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

Mairi M. Littleson, Christopher M. Baker, Anne J. Dalencon, Elizabeth C. Frye, Craig Jamieson, Alan R. Kennedy, Kenneth B. Ling, Matthew M. McLachlan, Mark G. Montgomery, Claire J. Russell, Allan J. B. Watson

Research output: Contribution to journalArticle

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.
LanguageEnglish
Number of pages14
JournalNature Communications
Publication statusAccepted/In press - 13 Feb 2018

Fingerprint

Agrochemicals
Structure-Activity Relationship
synthesis
Biological Products
Libraries
acids
determinants
templates
products
coronatine
coronafacic acid
Lead
1-amino-2-ethylcyclopropane-1-carboxylic acid
jasmonic acid

Keywords

  • phytotoxin coronatine
  • coronatine
  • food production
  • crop infestation

Cite this

Littleson, Mairi M. ; Baker, Christopher M. ; Dalencon, Anne J. ; Frye, Elizabeth C. ; Jamieson, Craig ; Kennedy, Alan R. ; Ling, Kenneth B. ; McLachlan, Matthew M. ; Montgomery, Mark G. ; Russell, Claire J. ; Watson, Allan J. B. / Scalable total synthesis and comprehensive structure–activity relationship studies of the phytotoxin coronatine. In: Nature Communications. 2018.
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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.",
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Littleson, MM, Baker, CM, Dalencon, AJ, Frye, EC, Jamieson, C, Kennedy, AR, Ling, KB, McLachlan, MM, Montgomery, MG, Russell, CJ & Watson, AJB 2018, 'Scalable total synthesis and comprehensive structure–activity relationship studies of the phytotoxin coronatine' Nature Communications.

Scalable total synthesis and comprehensive structure–activity relationship studies of the phytotoxin coronatine. / Littleson, Mairi M.; Baker, Christopher M.; Dalencon, Anne J.; Frye, Elizabeth C.; Jamieson, Craig; Kennedy, Alan R.; Ling, Kenneth B.; McLachlan, Matthew M.; Montgomery, Mark G.; Russell, Claire J.; Watson, Allan J. B.

In: Nature Communications, 13.02.2018.

Research output: Contribution to journalArticle

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AU - Jamieson, Craig

AU - Kennedy, Alan R.

AU - Ling, Kenneth B.

AU - McLachlan, Matthew M.

AU - Montgomery, Mark G.

AU - Russell, Claire J.

AU - Watson, Allan J. B.

PY - 2018/2/13

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