Hyperforin.

Hyperforin is a polyprenylated acylphloroglucinol derivative from Hypericum perforatum (St. John's wort). It exhibits antidepressant activity by a novel mechanism of action, antibiotic activity against gram-positive bacteria, and antitumoral activity in vivo. However, it also produces drug-drug interactions by activation of the pregnan X receptor. No total synthesis has been described. Some natural and semisynthetic analogues are available to study structure-activity relationships. Enzymatically, the skeleton of hyperforin is formed by isobutyrophenone synthase from isobutyryl-CoA and three molecules of malonyl-CoA. The first prenylation step is catalyzed by a soluble and ion-dependent dimethylallyltransferase. Hyperforin mainly accumulates in pistils and fruits where it probably serves as defensive compound.