Total Synthesis of All Eight Stereoisomers of α‐Tocopheryl Acetate. Determination of their diastereoisomeric and enantiomeric purity by gas chromatography

Abstract

Abstract All eight stereoisomers of α‐tocopheryl acetate have been synthesized in a state of high chemical and stereoisomeric purity. Key chiral side‐chain intermediates were prepared from (+)‐( S )‐3‐hydroxy‐2‐methylpropanoic acid. New routes to (2 R , 4′ RS , 8′ RS )‐α‐tocopheryl acetate, a mixture of four diastereoisomers, were also developed. A sensitive gas chromatographic method was developed to determine the diastereoisomeric and enantiomeric purity of α‐tocopherol samples as the methyl ethers. It was established for the first time that naturally occurring α‐tocopherol is essentially a single enantiomer (2 R , 4′ R , 8′ R ), synthetic all‐rac‐α‐tocopherol an equimolar mixture of four racemates, and that natural ( E )‐(7 R , 11 R )‐phytol is diastereoisomerically and enantiomerically homogeneous.