Humulupones A-F, Bitter Acid Derivatives from Humulus lupulus

Humulupones A-F (1-6), six new bitter acid derivatives with three types of new skeletons, were isolated from Humulus lupulus. Compounds 1-4 were four dimers with an unprecedented 6/6/6/6/6 pentacyclic skeleton featuring 6 stereogenic centers. Compounds 5 and 6 possessed an unreported 6/5/6 tricyclic ring system, with 5 consisting of spiro and bridged ring and 6 simultaneously incorporating bridged and fused ring systems. Their structures and absolute configurations were established by comprehensive spectroscopic analysis, DP4+ probability analyses, electronic circular dichroism, and X-ray diffraction analysis. Furthermore, compounds 1, 3, 4 and 6 showed anti-inflammatory effects in CuSO₄-induced zebrafish inflammatory model, and compounds 1-4 showed remarkable antiviral activities against herpes simplex virus type-1.