Tricyclic Polyprenylated Acylphloroglucinols from St John’s Wort, Hypericum perforatum

The new polyprenylated acylphloroglucinol derivatives 1 – 15 and the known furohyperforin ( 16 ) were isolated from the stems and leaves of Hypericum perforatum . Their structures were determined by analyses of NMR and HRESIMS data. Their absolute configurations were elucidated by a combination of electronic circular dichroism (ECD) and Rh 2 (OCOCF 3 ) 4 -induced ECD, as well as X-ray diffraction crystallography. The new hyperforatin F ( 9 ) contains a unique acetyl functionality at C-1 of the bicyclo[3.3.1]nonane core. Hyperforatins G ( 10 ) and H ( 11 ) are similarly the first examples of naturally occurring [3.3.1]-type polycyclic prenylated acylphloroglucinols possessing a carbonyl functionality at C-32. The compounds were tested for their acetylcholinesterase (AChE) inhibitory activities and cytotoxic activities against a panel of human tumor cell lines. Compounds 3, 5, 6, 8, and 9 exerted moderate inhibitory activities (IC 50 3.98–9.13 μM) against AChE.