Asymmetric Total Synthesis and Anti-Inflammatory Activity of Berbamine, Oxyacanthine, and Related Intermediates
The first asymmetric total synthesis of the bisbenzylisoquinoline alkaloids berbamine (<b>1a</b>) and oxyacanthine (<b>1b</b>) 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 <b>1a</b>, 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 <b>15a</b> displayed potent anti-inflammatory activity coupled with minimal cytotoxicity, emerging as a promising lead candidate for the development of novel anti-inflammatory agents.
Authors
- Jingshan Shen (ORCID: https://orcid.org/0000-0001-9679-9934)
- Khurshed A. Bozorov (ORCID: https://orcid.org/0000-0001-7449-0936)
- Haji Akber Aisa (ORCID: https://orcid.org/0000-0003-4652-6879)
- Temur A. Kushatov
- Feipu Yang (ORCID: https://orcid.org/0000-0003-2561-671X)
- Xiangrui Jiang (ORCID: https://orcid.org/0000-0001-5941-6105)
- Фарход Рузикулович Турсунов
- Jian‐Hua Qin (ORCID: https://orcid.org/0000-0003-0440-7759)
- Li Xiang (ORCID: https://orcid.org/0009-0009-4470-2315)
- Ozod Farmonov
Institutions
- Samarkand State University named after Sharof Rashidov (UZ)
- Xinjiang Medical University (CN)
- Chinese Academy of Sciences (CN)
- Institute of Organic Synthesis (RU)
- Xinjiang Technical Institute of Physics & Chemistry (CN)
- Culture Resource (EG)
- Shanghai Institute of Materia Medica (CN)
- Advanced Research Institute (US)
- Laboratoire de Synthèse Organique (FR)
- University of Chinese Academy of Sciences (CN)
- State Key Laboratory of Drug Research
Publication Details
- Journal
- Journal of Natural Products
- Published
- 2025-11-26
- DOI
- https://doi.org/10.1021/acs.jnatprod.5c01211
- Primary Topic
- Berberine and alkaloids research
- Type
- article
- Field-Weighted Citation Impact
- 0.00