Development of synthetic routes to D,L-α-tocopherol (vitamin E) from biologically produced geranylgeraniol

The use of the biologically derived diterpene alcohol geranylgeraniol was explored as an alternative to petrochemical-based isophytol as a side-chain synthon for producing D,L-alpha-tocopherol. Two routes were studied, both of which begin with allylic epoxidation followed by olefin hydrogenation to give epoxyphytol. Epoxyphytol can be reduced with Red-Al to provide phytan-1,3-diol which upon acid-catalyzed condensation with trimethylhydroquinone gives vitamin E in fair yield. In a higher-yielding process, epoxyphytol was deoxygenated with methylrhenium,trioxide/triphenylphosphine to generate a mixture of phytol and isophytol (>90% yield from geranylgeraniol). This mixture can serve as a plug-in replacement for isophytol in the final step of the currently practiced vitamin E chemistry. The use of methylrhenium trioxide to catalyse dehydration of vinyl dialkyl carbinols to 1,3-dienes was also demonstrated.