Analgesic sesquiterpenes from the roots of Rhododendron micranthum

Abstract

Two new guaiane-derived sesquiterpenes, rhodomicranins A−B (1−2), four new cadinane-type sesquiterpenes, rhodomicranins C–F (3−6), one new eudesmane-type sesquiterpene, rhodomicranin G (7), and nine known analogues (8−16) were isolated from the roots of Rhododendron micranthum. Compound 1 represent an unprecedented B-norguaiane sesquiterpene carbon skeleton. The structures and absolute configurations of the new compounds were determined unambiguously via spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism calculations. The plausible biosynthetic pathway for all compounds is proposed. Furthermore, the analgesic activities of compounds 1−16 were evaluated by an acetic acid-induced writhing test. At a dose of 1 mg/kg, compounds 2, 4−5, 9−10, 13, and 15 demonstrated significant analgesic effects with writhe inhibition rates ranging from 61.2% to 83.6%. In particular, compound 4 exhibited the highest potency of analgesic activity (1 mg/kg) with a writhe inhibition rate of 83.6%, equivalent to that produced by morphine at the same dose.