A NEW STEREOSELECTIVE SYNTHESIS OF (-)-ISOAVENACIOLIDE AND (-)-AVENACIOLIDE

The synthesis of isoavenaciolide and avenaciolide in their natural ena ntiomeric forms are described. In both syntheses, hio)-beta-[(methoxyc arbonyl)methyl]-gamma-lactones obtained by the base-induced cyclizatio n of enantiomerically enriched gamma-[(phenylthio)acyl] alpha,beta-uns aturated esters were used as starting materials. In the isoavenaciolid e synthesis the key step is the stereoselective hydroxylation of the e nolate generated in the (methoxycarbonyl)methyl chain that permits the bis-lactonization by a double transesterification. The configuration in the quaternary center vicinal to the carbonyl group in the ring was critical in order to obtain successfully the alpha-methylene lactone. In avenaciolide, the stereoselective synthesis of the bis-lactone uni t was performed taking advantage of the presence of the phenyl sulfide group which by previous activation was used as leaving group to obtai n the fused ring by an intramolecular substitution utilizing the carbo xylate of the beta-substituent as nucleophile. In this case, the alpha -methylene lactone was obtained by previously reported methodology.