Chemistry and Biology of the Polycyclic Polyprenylated Acylphloroglucinol Hyperforin

(+)-Hyperforin (1) is a polyprenylated acylphloroglucinol (PPAP) natural product isolated in 1971 from Hypericum perforatum. Also known as St. John's wort, Hypericum perforatum is a popular medicinal plant because of its antidepressant properties. (+)-Hyperforin (1) is the main component of the plant and has attracted the interest of the scientific community since it was identified as the agent responsible for the antidepressant activity. The subsequent discovery that it also displayed a wide range of biological activities triggered the interest of synthetic chemists because of its appealing, compact molecular structure. This microreview presents an overview of the synthetic studies reported so far for the racemic and enantioselective syntheses of (+)-hyperforin (1) and analogues, and attempts to shed light on the intriguing structure-activity relationships (SARs) of the natural product.