A Fast and Efficient MN-Approach for Reactivity of Natural Product Exploration in Plant Extract: Application to Diterpene Esters from Euphorbia dendroides

Natural products represent a rich source of bioactive compounds covering a large chemical space. Even if challenging, this diversity can be extended by applying chemical modifications. However, these studies require generally multigram amounts of isolated natural products and face frequent testing failures. To overcome this limitation, we propose a rapid and efficient approach that uses molecular networking (MN) to visualize new chemical diversity generated by simple chemical modifications of natural extract. Moreover, the strategy deployed enables the most appropriate reagents to be defined quickly upstream a reaction on a pure compound, in order to maximize chemical diversity. This methodology was applied to the latex extract of Euphorbia dendroides to follow the reactivity towards a series of acids and Lewis acids of three class of diterpene esters identified in this species: jatrophane, terracinolide, and phorbol. Through the molecular networking interpretation, in aim to illustrate our approach, two Lewis acids were selected for chemical modification on previously isolated jatrophane esters. Three rearranged compounds (3−5) were obtained when exposed to BF3.OEt2, showing that the most appropriate reagents can be selected by MN interpretation.