Starting from 4-hydroxy-5-methylcoumarin ( 7), (±)-preethulia coumarin (3) was synthesized in six steps and in 4% overall yield. The key synthetic procedure was a new type of Lewis acid catalysed, three-component Knoevenagel/hetero Diels-Alder reaction, which employs α-dicarbonyl com-Over the past few decades, an impressive variety of prenylated 5-methylcoumarins have been characterised, mainly from plants belonging to the Mutisieae tribus of the Compositae family. [1] These prenylated polyketides represent a significant addition to the shikimate-derived coumarins from umbelliferous and rutaceous plants, a class of compounds extensively investigated for their anticoagulant and phototoxic properties. [2] Interest in polyketide coumarins was sparked by the discovery of the powerful anthelmintic [3] and molluscicidal [4] properties of ethuliacoumarin A (1), a constituent of the Egyptian medicinal plant Ethulia conyzoides L. [5] The related analogues 2Ϫ4 were also isolated, [6] and some of them showed biological activity comparable to 1. [4] All these compounds share a 4,10-dimethyl-4-vinylpyrano[3,2-c]coumarin core, and only differ in the oxygenation of C-2 and the norprenyl residue. The powerful biological activity of these compounds suggests interaction with a host-specific target. This, however, remains unidentified, and the pharmacological potential of these compounds, though recognised, is still untapped. Ethuliacoumarins are