Three selected naturally occurring oxyprenylated secondary metabolites, namely 2-hydroxy4-isopentenyloxyacetophenone (1), 4-geranyloxy-2-hydroxyacetophenone (2), 4-farnesyloxyacetophenone (3), and derricidin (4) were synthesized and their inhibitory potency against soybean 15-lipoxygenase evaluated. Compounds 1 and 4 showed the most potent inhibitory activity with ICo50 values of 2.5 µM and 0.6 µM.