Humupulusones A and B, Two Skeletally Novel Acylphloroglucinol Derivatives from <i>Humulus lupulus</i>

Two novel acylphloroglucinol derivatives, humupulusones A and B (<b>1</b> and <b>2</b>), were isolated from <i>Humulus lupulus</i>. Compound <b>1</b>, a pair of enantiomers (<b>1a</b>/<b>1b</b>), is the first acylphloroglucinol derivative with a bicyclo[2.2.2] carbon skeleton possessing a novel 5/6/6/5/5 ring system. Humupulusone B (<b>2</b>), a pair of hemiacetal tautomers, features a highly rearranged 5/6/5-fused tricyclic scaffold. Moreover, <b>1a</b> and <b>2</b> exhibited significant inhibitory effects on LPS-induced NO production in BV-2 cells with IC₅₀ values of 13.55 and 16.09 μM, respectively.