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

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

doi:10.1038/s41467-018-03443-1

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

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

^*Corresponding author for this work

School of Chemistry

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	1105
Journal	Nature Communications
Volume	9
DOIs	https://doi.org/10.1038/s41467-018-03443-1
Publication status	Published - 16 Mar 2018

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Littleson, M. M., Baker, C. M., Dalençon, A. J., Frye, E. C., Jamieson, C., Kennedy, A. R., Ling, K. B., McLachlan, M. M., Montgomery, M. G., Russell, C. J., & Watson, A. J. B. (2018). Scalable total synthesis and comprehensive structure–activity relationship studies of the phytotoxin coronatine. Nature Communications, 9, Article 1105. https://doi.org/10.1038/s41467-018-03443-1

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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.",

author = "Littleson, {Mairi M.} and Baker, {Christopher M.} and Dalen{\c c}on, {Anne J.} and Frye, {Elizabeth C.} and Craig Jamieson 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.}",

note = "The authors thank the EPSRC UK National Mass Spectrometry Facility at Swansea University for analyses, the University of Strathclyde for PhD studentship (M.M.L), and Syngenta for financial and chemical support.",

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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.

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

Abstract

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