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[10.3.3.0 1,11 .0 4,9 .0 6,8 .0 14,17 ]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 IC 50 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.