TOTAL SYNTHESIS OF (-)-AUSTALIDE-B - A GENERIC SOLUTION TO ELABORATION OF THE PYRAN P-CRESOL BUTENOLIDE TRIAD

The toxic meroterpenoid (-)-austalide B has been prepared in its natur al form by chemical modification of the readily available optically ac tive enedione 11. Following stereocontrolled Robinson annulation to gi ve 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 obt ain 23 by Baeyer-Villiger oxidation. For the purpose of annealing ring s E and F, carbomethoxy trinate 41 was prepared and coupled to 42 thro ugh 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 sec ondary hydroxyl and inversion of its configuration delivered synthetic austalide B, which exhibited melting point, specific rotation, infrar ed, and NMR properties (H-1 and C-13) identical to the natural materia l obtained from South Africa.