Grayanane Diterpenoids from the Leaves of and Their Analgesic Activities.

Twenty-four grayanane diterpenoids (-) including 12 new ones (-) were isolated from . The structures of the new grayanane diterpenoids (-) were defined via extensive spectroscopic data analysis. The absolute configurations of compounds -, -, , and were established by single-crystal X-ray diffraction analysis, and electronic circular dichroism data were used to define the absolute configurations of auriculatols D () and E (). Auriculatol A () is the first example of a 5,20-epoxygrayanane diterpenoid bearing a 7-oxabicyclo[4.2.1]nonane motif and a ///-fused 5/5/7/6/5 pentacyclic ring system. Auriculatol B () is the first example of a 3α,5α-dihydroxy-1-β-grayanane diterpenoid. 19-Hydroxy-3--auriculatol B () and auriculatol C () represent the first examples of 19-hydroxygrayanane and grayan-5(6)-ene diterpenoids, respectively. Diterpenoids - showed analgesic activities in the writhing test induced by HOAc, and , , , , , and at a dose of 5.0 mg/kg exhibited significant analgesic effects (inhibition rates >50%). Grayanane diterpenoids grayanotoxins I () and IV () at doses of 0.2 and 0.04 mg/kg showed more potent analgesic activities than morphine.