Benzo-fused ten-membered ring meroterpenoids: sources, chemical diversity, biological activities, and biosynthesis

Meroterpenoids, a class of hybrid natural products derived from both terpenoid and non-terpenoid biosynthetic pathways, serve as a prolific source of drug leads, because of their structural complexity and extensive bioactivities. Meroterpenoids have provided many clinical drugs or promising leads, such as mycophenolic acid (an immunosuppressant), territrem B (an acetylcholinesterase inhibitor), and pyripyropene A (a cholesterol acyltransferase-2 inhibitor). Recently, meroterpenoids featuring a benzo-fused ten-membered ring skeleton have attracted considerable attention for their unique scaffolds and diverse post-modifications. Bioactivity evaluations have revealed that nearly half of these compounds (32 of 66) exhibit cytotoxicity with half-maximal inhibitory concentrations below 10 μM, and therefore have great potential as drug development candidates, particularly in cancer therapy. However, a systematic summary of this subclass remains lacking. Herein, we summarize benzo-fused ten-membered ring meroterpenoids reported between 1980 and 2024, including their sources, structural diversity, bioactivities, and biosynthetic pathways, to provide comprehensive insights to guide further studies on meroterpenoids.