Synthesis and of natural and nature inspired phlorotannins as potential sustainable extraction antifungal agents

Plant diseases are caused by pathogenic microorganisms, mainly fungi, which affect the quality and the yield of produced crops, causing losses up to the 30% at all stages of crop production. Pathogen control has been effectively performed mostly by synthetic fungicides. However, nowadays only a few of them are still allowed worldwide, and their consequent widespread use has resulted in both resistance emergence and spread in some pathogenic fungi1. Furthermore, synthetic pesticides have created a high environmental impact over the years, also causing bioaccumulation. To address the growing urgency in managing fungal diseases, there is the need to find new compounds able to effectively inhibit pathogens through known or novel mechanisms of action, and having lower human and environmental impact as well. In this framework, the development of natural and nature-derived agrochemicals is a promising approach. Recently phlorotannins emerged as a new class of polyphenolic compounds, which are present in the brown seaweed as a very complex mixture of phloroglucinol oligomers. Based on the promising antifungal activity showed by the crude extracts2, we developed a green microwave-assisted extraction to obtain enriched fractions of phenolic oligomers mixtures. Subsequently, phloroglucinol dimers, namely diphenylethers and biphenyls, and trimers were synthesised (Figure 1) to obtain highly pure single compounds with moderate to good yields. The potential antifungal activity of the single pure compounds and enriched fractions was investigated and compared. Furthermore, Differential Scanning Calorimetry (DSC) experiments were designed to study the potential interaction of the bioactives with the phospholipidic membrane3 of pathogenic fungi.