Humulupones A-F, Bitter Acid Derivatives from <i>Humulus lupulus</i>

Humulupones A<b>-</b>F (<b>1-6</b>), six new bitter acid derivatives with three types of new skeletons, were isolated from <i>Humulus lupulus</i>. Compounds <b>1-4</b> were four dimers with an unprecedented 6/6/6/6/6 pentacyclic skeleton featuring 6 stereogenic centers. Compounds <b>5</b> and <b>6</b> possessed an unreported 6/5/6 tricyclic ring system, with <b>5</b> consisting of spiro and bridged ring and <b>6</b> 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 <b>1</b>, <b>3</b>, <b>4</b> and <b>6</b> showed anti-inflammatory effects in CuSO₄-induced zebrafish inflammatory model, and compounds <b>1-4</b> showed remarkable antiviral activities against herpes simplex virus type-1.