Isolation, Structure Elucidation, Semi-Synthesis, And Structural Modification Of C-19-Diterpenoid Alkaloids From Aconitum Apetalum And Their Neuroprotective Activities

Five new aconitine-type C-19-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, 112a, 12b, 12d, 12e, 12k, 12m, 12n) with low cytotoxicity revealed compound 2 to exhibit good neuroprotective effects in H2O2-treated SH-SYSY cells at a concentration of 50 mu M. A series of studies using flow cytometry, staining, and Western blotting on 2 indicated that its neuroprotective effects may arise from inhibiting cell apoptosis.