Fengycin A Analogues with Enhanced Chemical Stability and Antifungal Properties.

Diana Gimenez,Aoife Phelan,Cormac D Murphy,Steven L Cobb

doi:10.1021/acs.orglett.1c01387

Diana Gimenez, Aoife Phelan + Show 2 more

Open Access

https://doi.org/10.1021/acs.orglett.1c01387

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Journal: Organic letters	Publication Date: Jun 2, 2021
Citations: 19	License type: CC BY 4.0

Affiliation: Durham University, University College Dublin

Abstract

Fengycins are cyclic lipo-depsipeptides produced by Bacillus spp. that display potent antifungal properties but are chemically unstable. This instability has meant that no total synthesis of any fengycin has been published. Here we report the synthesis of fengycin A analogues that display enhanced antifungal properties and chemical stability under both basic and acidic conditions. The analogues prepared also demonstrate that the fengycin core structure can be modified and simplified without the loss of antifungal activity.

Highlights

Fengycins are cyclic lipo-depsipeptides produced by Bacillus spp. that display potent antifungal properties but are chemically unstable
In particular fungal diseases, pose an increasing risk to global food security.[1−3] An important part of the crop protection arsenal is Bacillus subtilis strains, which are used as biological control agents (BCAs) (Serenade).[4−6] Bioactive Bacillus spp. are able to secrete, as an innate response to external microbiota stimuli, potent antimicrobial metabolites that include the cyclic lipopeptides (CliPs) from the iturin, surfactin, and fengycin families (Figure 1).[5,7−13] Fengycins are the dominant CliPs in Bacillus spp.[5,14,15] and are active against a range of phytopathogenic fungi,[12,16−19] causing cell lysis and leakage through binding with the plasma membrane
A further disadvantage relates to the fact that antifungal BCAs act slowly when compared to typical pests, and only give a very time-limited protection to crops.[21]. In light of these factors the application of individual bioactive CliPs, rather than the entire living organisms, would be an attractive option for the development of new crop protection agents. The problem with this strategy is that isolation and/or chemical synthesis of certain CliPs, like fengycin, has proven to be challenging

Summary

Introduction

Fengycins are cyclic lipo-depsipeptides produced by Bacillus spp. that display potent antifungal properties but are chemically unstable. To address the challenges associated with both the synthesis and stability of fengycins, we proposed to prepare a series of modified and simplified analogues (Figure 1B).

Results

Conclusion