Synthesis of Deoxyradicinin, an Inhibitor of Xylella fastidiosa and Liberibacter crescens, a Culturable Surrogate for Candidatus Liberibacter asiaticus

J Nat Prod. 2020 Jun 26;83(6):1810-1816. doi: 10.1021/acs.jnatprod.9b01207. Epub 2020 Jun 8.

Abstract

Pierce's disease of grapevine and citrus huanglongbing are caused by the bacterial pathogens Xylella fastidiosa and Candidatus Liberibacter asiaticus (CLas), respectively. Both pathogens reside within the plant vascular system, occluding water and nutrient transport, leading to a decrease in productivity and fruit marketability and ultimately death of their hosts. Field observations of apparently healthy plants in disease-affected vineyards and groves led to the hypothesis that natural products from endophytes may inhibit these bacterial pathogens. Previously, we showed that the natural product radicinin from Cochliobolus sp. inhibits X. fastidiosa. Herein we describe a chemical synthesis of deoxyradicinin and establish it as an inhibitor of both X. fastidiosa and Liberibacter crescens, a culturable surrogate for CLas. The key to this three-step route is a zinc-mediated enolate C-acylation, which allows for direct introduction of the propenyl side chain without extraneous redox manipulations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetylation
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology*
  • Citrus
  • Liberibacter / drug effects*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Oxidation-Reduction
  • Plant Diseases / microbiology
  • Pyrones / chemical synthesis*
  • Pyrones / chemistry
  • Pyrones / pharmacology*
  • Solubility
  • Vitis
  • Xylella / drug effects*

Substances

  • Anti-Bacterial Agents
  • Pyrones
  • deoxyradicinin

Supplementary concepts

  • Liberibacter crescens