Hyperforin

Hyperforin is a phytochemical produced by some of the members of the plant genus Hypericum, notably Hypericum perforatum (St John's wort). Hyperforin may be involved in the pharmacological effects of St. John's wort, specifically in its antidepressant effects. Hyperforin has only been found in significant amounts in Hypericum perforatum with other related species such as Hypericum calycinum containing lower levels of the phytochemical. It accumulates in oil glands, pistils, and fruits, probably as a plant defensive compound. The first natural extractions were done with ethanol and afforded a 7:1 yield of crude extract to phytochemical however, this technique produced a mixture of hyperforin and adhyperforin. The extraction technique has since been modernized using lipophilic liquid CO2 extraction to afford a 3:1 crude to phytochemical extraction which is then further purified away from adhyperforin. This CO2 extraction is rather tricky still because typical 'supercritical' conditions extract less material whereas anything over 40 °C (100°F) will degrade hyperforin. Other Hypericum species contain low amounts of hyperforin. Hyperforin is a prenylated phloroglucinol derivative and is a member of the Polycyclic polyprenylated acylphloroglucinol family, also known as the PPAP family. Hyperforin is a unique PPAP because it consists of a C8 quaternary stereocenter which was a synthetic challenge unlike other PPAP synthetic targets. The structure of hyperforin was elucidated by a research group from the Shemyakin Institute of Bio-organic Chemistry (USSR Academy of Sciences in Moscow) and published in 1975. A total synthesis of the non-natural hyperforin enantiomer was reported in 2010 which required approximately 50 synthetic transformations. In 2010, an enantioselective total synthesis of the correct enantiomer was disclosed. The retrosynthetic analysis was inspired by hyperforin's structural symmetry and biosynthetic pathway.