Structure ‐

Allelopathy and bioassays constitute fundamental tools in the search for new herbicide templates. The work described here is a continuation of a previous study focused on the structure–activity relationships between transport phenomena and phytotoxic activity. Different modifications were made to the naphthoquinone backbone and two key factors were identified as being responsible for changes in activity: lipophilicity and the nature of the functional group. The study of other naturally occurring and semi-synthetic naphthoquinones was also proposed. A total of 12 5-O-acyl plumbagins and 18 analogs with unsaturated and aromatic substituents at positions 2 and 5 were synthesized. These compoundswere evaluated in thewheat coleoptile bioassay and against Standard Target Species (STS) and three weeds, namely Echinochloa crus-galli L., Lolium rigidum Gaud. and Lolium perenne L. A strong structure–function relationship was observed for the different naphthoquinones and root and shoot length were the parameters that were most affected. Strong inhibitory effectswere observed for the isomeric forms 23 and 33 and the derivativeswith a free hydroxyl group, i.e. 24 and 30, gave values higher than 70% inhibition for root length in barnyardgrass and perennial ryegrass. These results highlight the potential of these compounds as models in the development of herbicides based on natural products