Structurally diverse diterpenoids from Pieris japonica as potent analgesics

Sixteen diterpenoids (1-16) including 10 new ones, pierisjaponins A-J (1-10), were isolated and identified from Pieris japonica, and their structures were classified into eight diverse carbon skeletons. Pierisjaponins A (1) and B (2) represent the first 1,5-seco-grayanane diterpenoid glucosides and only showed 17 carbon resonances instead of 26 carbons in the ¹³C NMR spectra, their structures were finally defined by single-crystal X-ray diffraction, and the unusual NMR phenomena were explained. Pierisjaponin E (5) is the first mollane diterpene glucoside. This is the first time to report ent-labdane (3, 4, and 11) and ent-rosane (15) type diterpenoids from the Ericaceae plants, which provided the precursors of the Ericaceae diterpenoids and enlarged the chemical diversity of Ericaceae diterpenoids. All the 16 isolates showed potent analgesic activities, and this is the first time to describe the analgesic activities of 1,5-seco-grayanane, ent-labdane, mollane, and ent-rosane type diterpenoids. A preliminary structure-activity relationship is discussed, which provided new clues to design novel analgesics based on the Ericaceae diterpenoids.