Elodeoidins A-H, acylphloroglucinol meroterpenoids possessing diverse rearranged skeletons from Hypericum elodeoides

Inspired by a geranyl-originated undecanoate acid ethyl ester (9), elodeoidins A-H (1-8) representing four unprecedented rearranged acylphloroglucinol meroterpenoids were discovered from the herb of Hypericum elodeoides. Their structures were elucidated by HRESIMS, NMR, Mosher, ECD, quantum chemical calculation, and biosynthetic pathway. Structurally, the sixmembered acylphloroglucinol core rearranged to five-membered β-diketone unit possessing an exocyclic carbonyl (C-1 or C-3) through α-ketol rearrangement. Subsequently, key cyclizations with C-1 or C-3 established a 2-cyclopentyltetrahydrofuran moiety in 1-2, a [5, 5]-spiroketal-fused 5-5-5-5 skeleton in 3-4, a 1, 2-dioxonane-bridged 5-9-5 framework in 5-7, and a 2,5-dioxabicyclo[2.2.2]octane caged structure in 8-9. (+)/(-)-5 and 6 showed significant anti-inflammatory activity (IC50: 6.06 ± 0.41 ~ 10.46 ± 0.14 μM). These diversiform skeletons indicated that the biosynthetic fragments inspired discovery and elucidation strategy is valuable for discovery of novel and unprecedented natural products.