Total Synthesis of Dinophysistoxin‐2 and 2‐epi‐Dinophysistoxin‐2 and Their PPase Inhibition

Okadaic acid (OA, 1) and its analogues—dinophysistoxin-1 (DTX-1, 2) and -2 (DTX-2, 3)—accumulated in mussels feeding on certain marine algae species, are causative agents of “diarrhetic shellfish poisoning” throughout the world. Okadaic acid and naturally occurring biosynthetic variants have demonstrated both potent protein serine-threonine phosphatase (PPase) inhibitory activities and apoptosisinducing activities among numerous cancerous cell lines. Circumstantially, these activities appear to be causally related. Thus, elucidating the structural basis of selective and potent OA-type PPase inhibition may underlie the discovery of novel anticancer leads. Herein, we disclose the first total synthesis of 3 and its nonnatural analogue 2-epi-3, and their PPase inhibitory activities.