Three rare anti-inflammatory sesquiterpene lactones from Magnolia grandiflora

Four new sesquiterpene lactones (SLs) (1–4), along with a biosynthetically related SL (5), have been isolated from the leaves of Magnolia grandiflora. Magrandate A (1) is notable as the first C18 homogemarane type SL, featuring a unique 1,7-dioxaspiro[4.4]nonan-6-one core. Compounds 2 and 3, representing the first instances of chlorine-substituted gemarane-type SL analogs in natural products, were also identified. The structures of these isolates were elucidated through a combination of spectroscopic data analysis, electronic circular dichroism calculations, and X-ray single-crystal diffraction analysis. All isolates demonstrated anti-inflammatory activity in lipopolysaccharide-stimulated RAW264.7 cells. Notably, 3–5 showed a significant inhibitory effect on nitric oxide production, with IC₅₀ values ranging from 0.79 to 4.73 μmol·L⁻¹. Additionally, 4 and 5 exhibited moderate cytotoxic activities against three cancer cell lines, with IC₅₀ values between 3.09 and 11.23 μmol·L⁻¹.