Pierisformotoxins A-D, Polyesterified Grayanane Diterpenoids from Pieris formosa and Their cAMP-Decreasing Activities

Four highly acylated diterpenoids, designated as pierisformotoxins A-D (1-4, resp.), along with 26 known compounds, were isolated from the flowers of Pieris formosa. Among them, pierisformotoxins A and B (1 and 2, resp.) were new highly acylated grayanane diterpenoids, of which the five-membered ring A has undergone an oxidative cleavage between C(3) and C(4), followed by lactonization, to give rise to a five-membered lactone ring between C(3) and C(5), differing from the previously reported grayanane diterpenoids with a 5/7/6/5 ring system. Results of the cAMP-regulation-activity assay showed that pierisformotoxin C (3) at 10M (inhibitory ratio (IR): 10.1%) or 2M (9.8%), and pierisformotoxin B (2) at 50M (13.9%) significantly decreased the cAMP level in N1E-115 neuroblastoma cells (p<0.05).