Syntheses of a-Tocopherol

The purpose of this paper is to give a brief survey on syntheses and chemical transformations of vitamin E. Special emphasis will be laid on methods suitable for labeling of the tocopherols. Except for a-, jS-, 7-, and 6-tocopherol, the tocol nomenclature proposed by Karrer and Fritzsche (1938) will be used throughout this review. 

The earlier synthetic work in the vitamin E field has been reviewed by Karrer (1939),. John (1939), Todd (1939), Karrer and Bergel (1939), Smith 

The technical syntheses are based on the condensation of phytol or isophytol with trimethylhydroquinone, which can be prepared from 3,5-dimethylphenol by the Mannich reaction followed by a series of obvious steps. We prepared radioactive C -labelcd trimethylhydroquinone (specific activity 11.8 ic/mg), os shown in Fig. 2. 

Further condensation with natural phytol, e.g., in the presence of zinc chloride (Fig. 3) gave (2RS 4 R 8 R)-a-tocopherol (specific activity of the acetate 3.85 /lo/mg). With isophytol synthesized from acetone, totally racemic a-tocopherol (specific activity of the acetate 4.3 M /mg) was ob- 

In 1942 two further methods for preparing a-tocopherol were published (Fig. 4). The essential step in the synthesis developed by John and Pini (1942) was the Grignard reaction of the aromatic ketone (I) with hexahy-drofarnesylmethylmagnesium bromide (II). After several further steps, totally racemic a-tocopherol was obtained. Smith and Miller (1942) used the C18-ketone (IV), prepared by ozonolysis of natural phytol and the aromatic Grignard compound (III) to get finally (2RS 4 R 8 R)-a-toco-pherol. 

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Three new total syntheses of a-tocopherol (Vitamin E) have appeared, all depending on the construction of chiral chromans. The synthesis of a key... 

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