Hyperacmoses A–C, Three Seco-Norpolyprenylated Acylphloroglucinols from Hypericum acmosepalum with Lipid-Lowering Activity

Hyperacmoses A-C, three seco-norpolyprenylated acylphloroglucinols (PPAPs) (1-3), along with two processors (4 and 5), were purified from Hypericum acmosepalum. Structurally, compounds 1 and 2 represent the first seco-norPPAP with an unprecedented 5/6/5/6/5 pentacyclic framework, while compound 3 is the first seco-norPPAP with a 5/5/6/6 tetracyclic core. Three rare PPAPs had the same biosynthetic precursor, and Baeyer-Villiger oxidation of this precursor at different positions could finally give different types of PPAPs (1-3). Four compounds (1, 2, 4, and 5) exhibited a better triglyceride (TG) inhibitory effect than atorvastatin in oleic acid-induced HepG2 cells. The compound with the highest potential, compound 1, could prohibit the expression of lipid synthesis proteins, FASN and ACACA, by targeting ACSS2.