Analgesic Grayanane-Derived Diterpenoids from the Flowers of Rhododendron molle

Ten new grayanane-derived diterpenoids, rhodomollein LVII-LXVI (1-10), along with the known compound rhodomollein XLIII (11), were isolated from the flowers of Rhododendron molle. Their structures were elucidated by detailed spectroscopic analysis, X-ray diffraction crystallography, and ECD calculations. Rhodomollein LVII-LIX (1-3) are the first-discovered 3-O-(E)-p-coumaroylquinic acid, nicotinic acid, and 2-furoic acid derivatives of grayanane diterpenoids, respectively. In an acetic acid-induced writhing test, compounds 1 and 3 demonstrated significant antinociceptive effects with writhing inhibition rates of 77.2% and 71.5%, respectively, at a dose of 0.2 mg/kg. Compound 1 was found to be twice as potent as morphine, exhibiting significantly lower toxicity (LD50 = 130.90 mg/kg, i.p.) compared to rhodojaponin VI (LD50 = 1.79 mg/kg, i.p.).