Hyperterpenoids A and B: Two pairs of unprecedented 6/6/4/6/6 polycyclic cyclobutane meroterpenoids with potent neuroprotective and anti-inflammatory activities from Hypericum beanii

Hyperterpenoid A (1) and B (2), two pairs of enantiomers, with an unprecedented 6/6/4/6/6 polycyclic skeleton, along with one known compoud hypermonone A (3) were isolated from Hypericum beanii. The racemate (+/-)-1 and (+/-)-2 were successfully separated into the two optically pure enantiomers (ee >= 99%) using a preparative HPLC system. Their absolute configurations were elucidated by extensive spectroscopic analyses and single-crystal X-ray diffraction method. The related plausible biogenetic pathways were presented. Compound 1-3 showed significant neuroprotective activity and potential anti-inflammatory activity. The result that (+)-2 and (-)-2 presented different anti-inflammatory properties, may lead us to new discovery of structure activity relationship between racemates, enantiomers, and diastereomers, as well as further research regarding the binding of drugs to target proteins. (C) 2021 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.