Analgesic Grayanane-Derived Diterpenoids from the Flowers of <i>Rhododendron molle</i>

Ten new grayanane-derived diterpenoids, rhodomollein LVII-LXVI (<b>1</b>-<b>10</b>), along with the known compound rhodomollein XLIII (<b>11</b>), were isolated from the flowers of <i>Rhododendron molle</i>. Their structures were elucidated by detailed spectroscopic analysis, X-ray diffraction crystallography, and ECD calculations. Rhodomollein LVII-LIX (<b>1</b>-<b>3</b>) are the first-discovered 3-<i>O</i>-<i>(E)</i>-<i>p</i>-coumaroylquinic acid, nicotinic acid, and 2-furoic acid derivatives of grayanane diterpenoids, respectively. In an acetic acid-induced writhing test, compounds <b>1</b> and <b>3</b> demonstrated significant antinociceptive effects with writhing inhibition rates of 77.2% and 71.5%, respectively, at a dose of 0.2 mg/kg. Compound <b>1</b> 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.).