Antinociceptive grayanane-derived diterpenoids from flowers of Rhododendron molle

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Twelve new grayanoids (1-12) along with five known compounds were isolated from flowers of Rhododendron molle.Their structures were fully characterized using a combination of spectroscopic analyses,computational calculations,and single crystal X-ray diffraction.Rhomollone A (1)possesses an unprecedented 5/6/6/5 tetra-cyclic ring system (B-nor grayanane) incorporating a cyclopentene-l,3-dione scaffold.Rhodomollein XLⅢI (2) is a dimeric grayanoid,containing a novel 14-membered heterocyclic ring with a C2 symmetry axis.The antinociceptive activities of compounds 3,4,6,7,and 12 -17 were evaluated by an acetic acid-induced writhing test.Among them,compounds 3,7,12,15 and 16 displayed significant antinociceptive activities at a dose of 20 mg/kg with inhibition rates ranging from 41.9% to 91.6%.Compounds 6 and 13 inhibited 46.0% and 39.4% of the acetic acid-induced writhes at a dose of 2 mg/kg,while compound 17 inhibited 34.3% of the writhes at a dose of 0.4 mg/kg.
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