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

  • J Nat Prod. 2025 Dec 26;88(12):2947-2959. doi: 10.1021/acs.jnatprod.5c01211.
Li Xiang  1  2  3 ,  Jishan Qin  2  3 ,  Temur Kushatov  4 ,  Firdavsi Tursunov  4 ,  Ozod Farmonov  2  3 ,  Xiangrui Jiang  2  3  5 ,  Feipu Yang  2 ,  Jingshan Shen  2  3 ,  Khurshed Bozorov  4 ,  Haji Akber Aisa  1  3  6
Affiliations
  • 1. State 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.
  • 2. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P. R. China.
  • 3. University of Chinese Academy of Sciences, Beijing 10049, P. R. China.
  • 4. Department of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, Samarkand 140104, Uzbekistan.
  • 5. Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong 264117, P. R. China.
  • 6. School of Pharmacy, Xinjiang Medical University, Urumqi 830054, P. R. China.
PMID: 41292297 DOI: 10.1021/acs.jnatprod.5c01211
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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