Isolation, Structure Elucidation, Semi-Synthesis, and Structural Modification of C<sub>19</sub>-Diterpenoid Alkaloids from <i>Aconitum apetalum</i> and Their Neuroprotective Activities
Lin‐Xi Wan, Ji-Fa Zhang, Yongqi Zhen, Lan Zhang, Xiaohuan Li, Feng Gao, Xian‐Li Zhou
Abstract
Five new aconitine-type C19-diterpenoid alkaloids, apetalrines A–E (1–5), were isolated from Aconitum apetalum. Their structures were determined by analysis of 1D and 2D NMR, IR, and HRESIMS data. Semisynthesis of apetalrine B (2) from its parent compound aconorine was achieved to confirm the structure proposed. Twenty derivatives of 2 (11a–11l, 12a, 12b, 12d, 12e, 12j, 12k, 12m, 12n) were synthesized via a unified approach relying on simple coupling reactions. The evaluation of neuroprotective effects of compounds (1–5, 11b, 11c, 11f–11i, 12a, 12b, 12d, 12e, 12k, 12m, 12n) with low cytotoxicity revealed compound 2 to exhibit good neuroprotective effects in H2O2-treated SH-SY5Y cells at a concentration of 50 μM. A series of studies using flow cytometry, staining, and Western blotting on 2 indicated that its neuroprotective effects may arise from inhibiting cell apoptosis.