Analgesic diterpenoids with diverse carbon skeletons from the leaves of Rhododendron auriculatum.

Sixteen diterpenoids including nine undescribed ones, named rhodoauriculatols A−I, were isolated from the leaves of Rhododendron auriculatum Hemsl. Sixteen diterpenoids belong to seven diverse carbon skeletons, which were classified into 1,10-seco-grayanane, 1,10:2,3-diseco-grayanane, A-homo-B-nor-ent-kaurane, ent-kaurane, 4,5-seco-ent-kaurane, leucothane, and grayanane, respectively. Their structures were determined by the detailed HRESIMS, 1D and 2D NMR, UV, and IR data analysis, and their absolute configurations were established by single crystal X-ray diffraction analysis, electronic circular dichroism (ECD) data analysis, ECD calculation, as well as chemical methods. Rhodoauriculatols A−C possess a rare 1,10-seco-grayanane diterpene skeleton. Rhodoauriculatol D is the second example of the 1,10:2,3-diseco-grayanane diterpenoids, and rhodoauriculatol E is the fourth example of the A-homo-B-nor-ent-kaurane diterpenoids. Rhodomicranone E was reported as a natural product for the first time. All the isolated sixteen diterpenoids showed analgesic activities in the acetic acid-induced writhing test. Rhodoauriculatols B, E−G, rhodomicranone E, pierisformoside F, and micranthanoside A showed significant analgesic activities with the inhibition rates over 40%, and their preliminary structures-activity relationships were studied.