Design, Synthesis, and Anti‐Inflammation Activity of C‐12 Arylated Tetrahydropalmatine Derivatives

Structural optimization of natural products provides an important way for new drug discovery. The bioactive natural product L ‐tetrahydropalmatine and its analogs have attracted significant attention due to their potent pharmacological activities. In this study, a library of novel C12‐arylated L ‐tetrahydropalmatine derivatives ( 4a – 4ad ) was synthesized via Pd‐catalyzed Suzuki–Miyaura cross‐coupling reaction. Among these derivatives, compound 4p, bearing a 4‐ethenylphenyl moiety, suppressed the production of pro‐inflammatory cytokines (TNF‐α and IL‐1β) in LPS‐induced in vitro inflammatory models, indicating that it might be a potential anti‐inflammatory agent. This work offers valuable insights into the development of tetrahydropalmatine analogs as novel anti‐inflammatory agents.