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.