Total synthesis of a salicylihalamide analogue

One of the first selective mammalian V-ATPase inhibitors isolated and synthesized, salicylihalamide A is a member of a novel benzolactone enamide pharmacophore family from marine source. Previous reports on structure and activity studies have mostly concentrated on modifying enamide side chains and/or substituents on the macrolactone ring. Here a total synthesis of an analogue of salicylihalamide A with a truncated lactone ring is described in an effort to better understand the role that the macrolactone ring plays in its biological activity. Different side chain preparation and installation strategies are explored and compared as well.*; *Please refer to dissertation for diagrams.