Hyperacmosins K–M (1–3), three new polycyclic polyprenylated acylphloroglucinol (PPAPs) derivatives, were isolated from the air-dried aerial parts of Hypericum asmosepalum. Compounds 1 and 2 both possessed a rare 5,5-spiroketal subunit with the loss of C-2′ carbonyl in the phloroglucinal ring, while compound 3 featured an unusual 1,2-seco-bicyclo[3.3.1] PPAP skeleton. Their structures were confirmed by NMR, HRESIMS, and CD spectra. The plausible biogenetic pathways of 1–3 were proposed, which gave an insight for future biomimetic synthesis of the novel compounds.