The plant metabolite, equiselignan B (2), isolated from the fruits of Styrax suberifolius was used to generate a semisynthetic library. Extraction and purification studies yielded large quantities (∼70 mg) of 2, a new glycoside, suberifolioside A (1), and the previously described neolignan egonol (3). The planer structure of 1 was established following 1D/2D NMR and MS analyses, and its absolute configuration was determined by X-ray diffraction studies. Acid hydrolysis of 1 yielded an additional amount of scaffold 2 (436 mg) that was subsequently converted into seven new ether derivatives (4–10) and two new ester derivatives (11–12) using commercially available alkyl halides and acyl chlorides, respectively. The chemical structures of the new semisynthetic ether and ester derivatives were assigned by spectroscopic and spectrometric analyses. Subsequently, compounds 1–12 were evaluated for their anthelmintic activity on exsheathed third-stage larvae (xL3s) and fourth-stage larvae (L4s) of Haemonchus contortus (barber's pole worm) – a highly pathogenic parasitic roundworm of ruminant livestock. Ether derivative 5 displayed significant anthelmintic activity against both xL3s and L4s, resulting in a 66–73 % reduction in motility at 50 μM after 168 h (xL3s) or 90 h (L4s) of exposure and IC50 values of 24–30 μM. This derivative also induced curved (Cur), evisceration (Evi) and skinny (Ski) phenotypes in affected larvae. Compounds 1, 9 and 12 also had marked activity against L4s, which indicate that the neolignan structure class warrants further investigation for anthelmintic activity.