Anti-inflammatory Grayanane Diterpenoids from the Leaves of Rhododendron molle

Thirteen new grayanane diterpenoids (1–13), a new dimeric grayanane diterpenoid, bimollfoliagein A (14), and 15 known analogues (15–29) were isolated from the leaves of Rhododendron molle. The structures of the new compounds (1–14) were determined by extensive spectroscopic data interpretation. The absolute configurations of 1–3, 7, 8, 16, 18, and 24 were defined by single-crystal X-ray diffraction analysis. Mollfoliagein A (1) represents the first example of a 2,3:11,16-diepoxy grayanane diterpenoid, featuring a cis/trans/cis/cis/trans-fused 3/5/7/6/5/5 hexacyclic ring system with a 7,13-dioxahexacyclo­[10.3.3.01,11.04,9.06,8.014,17]­octadecane scaffold. Diterpenoids 1–29 were evaluated for their anti-inflammatory activities in vitro, and 15, 16, 18, 19, 23–26, 28, and 29 exhibited significant inhibitory activities against nitric oxide production in lipopolysaccharide-induced RAW264.7 mouse macrophages with IC50 values ranging from 2.8 to 35.4 μM. A preliminary structure–activity relationship for the anti-inflammatory activity of diterpenoids 1–29 is discussed.