Novel glutamic acid derivatives from the bulbs of Fritillaria verticillate Willd and their antitumor activities

Four previously undescribed glutamic acid derivatives, verticillamines A-D (1–4), together with six known compounds (5–10) were isolated from the bulbs of Fritillaria verticillate Willd. The structures of (1−10) were established on the basis of UV, IR, MS, 1D and 2D NMR, and the absolute configurations of compounds (1–4) were determined by calculated ECD methods. Among them, compounds (1–3) were rare 2-methyl-γ-lactam alkaloid derivatives. Moreover, both γ-lactam alkaloids (1–5) and pyrrolidine alkaloids (6–7) were discovered in Fritillaria for the first time. Compound 8 exhibited moderate cytotoxic activities against A2780 and HepG 2 cells, with IC50 values of 11.7 ± 5.2 μM and 25.6 ± 2.8 μM.