The toxic meroterpenoid (-)-austalide B has been prepared in its natural form by chemical modification of the readily available optically active enedione 11. Following stereocontrolled Robinson annulation to give 13 and fully regiocontrolled gem-dimethylation of this intermediate, the highly functionalized tetracyclic ortho ester 22 was produced in four additional steps. At this point, it proved an easy matter to obtain 23 by Baeyer-Villiger oxidation. For the purpose of annealing rings E and F, carbomethoxy trinate 41 was prepared and coupled to 42 through the agency of Pd-2(dba)(3) and (furyl)(3)P. With arrival at 39, it proved possible by sequential intramolecular Claisen condensation, O-methylation, and modest warming to produce 50. Deprotection of the secondary hydroxyl and inversion of its configuration delivered synthetic austalide B, which exhibited melting point, specific rotation, infrared, and NMR properties (H-1 and C-13) identical to the natural material obtained from South Africa.