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Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine
Published on: June 13, 2022
Asymmetric Total Synthesis and Anti-Inflammatory Activity of Berbamine, Oxyacanthine, and Related Intermediates
Li Xiang1,2,3, Jishan Qin2,3, Temur Kushatov4
1State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, P. R. China.
Abstract:
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.
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