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Updated: Jun 8, 2025

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Synthesis and Biological Activity of Tetracyclic Dispiro Core Derivatives of Natural Products Dispirocochlearoids A-C
Junping Pei1,2, Ying Wang1, Shengjie Shi1
1Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong 264117, China.
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 anti-inflammatory 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 (IC50 = 2.8 μM).
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