Total Syntheses of Marrubiin and Related Labdane Diterpene Lactones

Total syntheses of the labdane diterpene lactones marrubiin, marrulibacetal, desertine, marrulibacetal A, marrubasch F, cyllenine C, marrulanic acid, and marrulactone are described. The -decalin moiety of these molecules was constructed in a stereoselective manner by a Pauson-Khand reaction, and the resultant cyclopentenone was oxidatively cleaved for formation of the lactone ring. Elongation of the side chain at C9 was achieved by an epoxide-opening reaction with a variety of nucleophiles, and the functional group manipulations completed the syntheses of these natural products. Stereochemistries of desertine could be established by the transformations.