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.