Total Synthesis of (+)-Antrocin and Its Diastereomer and Clarification of the Absolute Stereochemistry of (-)-Antrocin.

Using 2,2-dimethyl cyclohexanone as the starting compound, (+)-antrocin and its diastereomer have been synthesized. The absolute stereochemistry of (-)-antrocin, a natural sesqui-terpenoid and an antagonist in some types of cancer cells, was clarified using the character data of (+)-antrocin. The synthetic procedure involved two key steps: (1) the reaction of vinyl magnesium bromide with 2,2-dimethyl-6-t-butyl-dimethyl-silyoxy-methyl-1-cyclo-hexanone to give a vinyl cyclohexanol derivative and (2) a highly stereoselective intramolecular Diels-Alder (IMDA) reaction of the camphanate-containing triene intermediate. The relative energy levels of the possible transition states of the IMDA reaction of the camphanate-containing triene were obtained from density functional theory calculations, proving the stereospecific formation of the target molecule.