Total synthesis of natural dysidiolide

Dysidiolide (1), a novel sesterterpenoid previously isolated from the Carib bean sponge Dysidea etheria de Laubenfels, inhibits the action of the prote in phosphatase, cdc25A. The authors establish a novel total synthesis of na tural dysidiolide (1) using intramolecular Diels-Alder reaction as the key step from optically active cyclohexenone 3. Decalin, the core structure of 1, was constructed by intramolecular Diels-Alder reaction of the diene este r generated by elimination of the phenyl sulfoxide group from sulfoxide est er 6 prepared from cyclohexenone 3. Diastereoselective methylation at C-7, alkylation at C-6, and deoxygenation of C-12 and C-24 positions gave the fu lly substituted bicyclic core of 1. The two side chains of the bicyclic cor e were further extended so as to afford natural dysidiolide (1). The total yield of this synthesis exceeds that of previous syntheses of 1.