Stylosines A and B, anti-inflammatory diterpenoid alkaloids from Aconitum stylosum

Two previously undescribed seco-type C19-diterpenoid alkaloids, stylosines A and B (1–2), which possess an unprecedented opened D ring by the C(15)–C(16) broken bond forming a five-membered C(15)−O–C(14) lactone ring, together with 14 known diterpenoid alkaloids were isolated from the roots of Aconitum stylosum (Ranunculaceae). Compound 1 is the first reported C19-diterpenoid alkaloid with an α-orientation at H-13. Their structures were determined by extensive spectroscopic analyses, NMR calculations and DP4+ analysis. A plausible biosynthetic pathway of the undescribed compounds was proposed. Compounds 1 and 2 showed significant inhibitory activity against the production of inflammatory cytokines (interleukin 1β, cyclooxygenase-2, and tumor necrosis factor α) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Compounds 1 and 2 exhibited antibacterial activity against Staphylococcus aureus with MIC values of 2.00 and 32.00 μg/mL, respectively. [Display omitted] •Stylosines A and B (1–2), which possess an unprecedented opened D ring by the C(15)–C(16) broken bond forming a five-membered C(15)−O–C(14) lactone ring.•Compound 1 is the first reported C19-diterpenoid alkaloid with α-orientation at H-13.•Compounds 1 and 2 showed significant anti-inflammatory effects.•Compounds 1 and 2 exhibited antibacterial activity against Staphylococcus aureus.