Asymmetric Total Synthesis and Anti-Inflammatory Activity of Berbamine, Oxyacanthine, and Related Intermediates

The first asymmetric total synthesis of the bisbenzylisoquinoline
alkaloids berbamine (1a) and oxyacanthine (1b) has been accomplished by employing Noyori asymmetric hydrogenation
for chirality installation and leveraging copper-mediated Ullmann
coupling for macrocycle formation. Our synthesis unequivocally confirmed
the sample misidentification of 1a, as indicated in our
previous work. Evaluation of anti-inflammatory activities revealed
that both synthetic and natural berbamine or oxyacanthine comparably
suppressed gene expression of pro-inflammatory cytokines IL-6 and
IL-1β in LPS-stimulated RAW 264.7 macrophages. Notably, intermediate 15a displayed potent anti-inflammatory activity coupled with
minimal cytotoxicity, emerging as a promising lead candidate for the
development of novel anti-inflammatory agents.