An improved synthesis of (−)-brevisamide, a marine monocyclic ether amide of dinoflagellate origin

An improved synthesis of (−)-brevisamide a marine cyclic ether isolated from the red-tide dinoflagellate Karenia brevis was achieved. The ether ring portion was constructed from an unsaturated lactone, which was prepared enantioselectively via an Evans aldol reaction and one-pot lactonization in the presence of excessive base after an Ando reaction. The ether ring and a dienol side chain fragment were connected via Suzuki-Miyaura coupling.