Hypermogins A–D, four highly modified polycyclic polyprenylated acylphloroglucinols from Hypericum monogynum

[Display omitted] •Four new polycyclic polyprenylated acylphloroglucinols were isolated from Hypericum monogynum.•Hypermogins A–D (1–4) were characterized by an unusual 6,5,5-tricyclic system.•All compounds exhibited significant reversal activity on MCF-7/ADR. Four highly modified polycyclic polyprenylated acylphloroglucinols (PPAPs) with an unusual 6,5,5-tricyclic system, hypermogins A–D (1–4), together with one known analogue (5), were isolated from the flowers of Hypericum monogynum. From a possible biogenic synthesis pathway analysis, compounds 2 and 3 could be obtained by oxidation of a double bond and hydrolysis for 1 and 5. In addition, compound 3 might undergo a pinacol rearrangement to produce compound 4. The structures of the isolates were determined by comprehensive MS, NMR spectroscopy and electronic circular dichroism (ECD) calculations. All compounds significantly reversed multidrug resistance in MCF-7/ADR cells.