Five new aconitine-type C19-diterpenoid alkaloids, apetalrines A-E (1-5), were isolated fromAconitum 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 of2(11a-11l12a12b12d12e12j12k12m12n) were synthesized via a unified approach relying on simple coupling reactions. The evaluation of neuroprotective effects of compounds (1-511b11c11f-11i12a12b12d12e12k12m12n) with low cytotoxicity revealed compound2to 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 on2indicated that its neuroprotective effects may arise from inhibiting cell apoptosis. © 2021 American Chemical Society and American Society of Pharmacognosy