Synthesis and Biological Activity of Tetracyclic Dispiro Core Derivatives of Natural Products Dispirocochlearoids A–C

Abstract

Natural products dispirocochlearoids A−C, which are meroterpenoids derived from Ganoderma fungi, feature a 6/6/5/6/6/6 ring system and exhibit selective COX-2 inhibitory activity. Herein, the concise total synthesis of the tetracyclic core structure of dispirocochlearoids A−C was achieved through an aldol reaction/cyclization/ deprotection/cyclization cascade sequence. A series of simplified tetracyclic analogues was successfully constructed and their antiinflammatory activity was further explored, with several tetracyclic analogues (such as compound 8ab) exhibiting strong inhibitory activity against IL-1β expression in lipopolysaccharide-stimulated bone marrow-derived macrophage cells (IC 50 = 2.8 μM).