Total Syntheses of (+)-Acutiphycin and (+)-trans-20,21-Didehydroacutiphycin

The first total syntheses of the cytotoxic macrolides (+)-acutiphycin ( 1 ) and (+)- trans -20,21-didehydroacutiphycin ( 2 ) have been achieved. An acyclic stereocontrol strategy was employed to establish the configurations at C(5), C(10), and C(13) as well as the E geometry of the C(8,9)-trisubstituted olefin. Importantly, the natural source of 1 and 2, the blue-green alga Osillatoria acutissima, no longer produces these metabolites.