Structurally diverse alkaloids from Buxus sempervirens with cardioprotective activity

• Published in: Bioorganic chemistry 2021-04, Vol.109, p.104753-104753, Article 104753
• Main Authors: Xiang, Zhi-Nan, Su, Jun-Cheng, Liu, Yi-Hui, Deng, Bin, Zhao, Ning, Pan, Jun, Hu, Zhuo-Fan, Chen, Fei-Hong, Cheng, Bing-Yu, Chen, Jia-Chun, Wan, Luo-Sheng
• Format: Article
• Language: English
• Subjects: Buxus; Buxus alkaloid; Buxus sempervirens; Cardioprotective effect
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2021.104753

Extensive phytochemical study of the methanol extract of twigs and leaves of Buxus sempervirens resulted in the identification of 17 Buxus alkaloids, including 12 new ones, namely buxusemines A–L (1–12). Their structures were delineated by detailed analysis of the HRESIMS and NMR data, as well as quantum chemical NMR calculations. Buxusemine A (1) represents the second Buxus alkaloid with a unique spiro[4.6]undecatriene moiety, buxusemines B–C (2–3) are a rarely occurring class of Buxus alkaloids featured with an additional five-membered ring through the ether or lactone linkage between C-10 and C-23, and buxusemines D–F (4–6) are another rare type of Buxus alkaloids with an epoxy motif. In the assessment of their bioactivities, buxusemine F (6) and buxanoldine (17) displayed more potent protective effects than the positive control cyclovirobuxinum D in the doxorubicin-induced cardiac injury model. [Display omitted] •17 Buxus alkaloids, including 12 new ones, were isolated from B. sempervirens.•Buxusemine A represents the second Buxus alkaloid with a spiro motif.•Buxusemines B−F are also members of two rare occurring substructures of Buxus alkaloids.•All the isolates were evaluated for their cardioprotective activities.•Preliminary structure-activity relationships were discussed. Extensive phytochemical study of the methanol extract of twigs and leaves of Buxus sempervirens resulted in the identification of 17 Buxus alkaloids, including 12 new ones, namely buxusemines A–L (1–12). Their structures were delineated by detailed analysis of the HRESIMS and NMR data, as well as quantum chemical NMR calculations. Buxusemine A (1) represents the second Buxus alkaloid with a unique spiro[4.6]undecatriene moiety, buxusemines B–C (2–3) are a rarely occurring class of Buxus alkaloids featured with an additional five-membered ring through the ether or lactone linkage between C-10 and C-23, and buxusemines D–F (4–6) are another rare type of Buxus alkaloids with an epoxy motif. In the assessment of their bioactivities, buxusemine F (6) and buxanoldine (17) displayed more potent protective effects than the positive control cyclovirobuxinum D in the doxorubicin-induced cardiac injury model.