VITAMIN RESEARCH 



is inactivated by vigorous treatment with acid or alkali, is not an a- 

 amino acid, is not destroyed by acylating or alkylating reagents, and 

 is easily oxidized. 



Not all of the well-known vitamins have had their constitution 

 elucidated by an application and development of micro methods. The 

 correct structure of a-tocopherol of the vitamin E group was deter- 

 mined largely by interpretation of the results of three chemical reac- 

 tions, which were carried out on 2.1, 4.3, and 25 grams of the vitamin 

 in each case. While repeating some of the isolation work of a-toco- 

 pherol from cottonseed oil described by Emerson, Emerson, and 

 Evans (7), the late Dr. E. Fernholz, working in the laboratory adjoin- 

 ing that of the author, intimated that he desired to accumulate enough 

 of the a-tocopherol to permit reactions on a gram-scale basis. It was 

 feasible to isolate a-tocopherol on this scale. Subsequently, Fernholz 

 described (8) the thermal decomposition of a-tocopherol which yielded 

 durohydroquinone, and the details (9) of the experiment reveal that 

 2.1 g. of the vitamin had been heated for six hours at 355°. The 

 crystalline sublimate yielded 257 mg., or 67%, of durohydroquinone 

 and a hydrocarbon of the composition Ci8-i9H36- This characteriza- 

 tion of durohydroquinone shattered the frequently discussed idea that 

 a-tocopherol is related to the sterols. The absorption spectra and 

 chemical properties of some synthetic monoethers of durohydro- 

 quinone, when considered in conjunction with other suggestive evi- 

 dence, led to the hypothesis that a-tocopherol was derived from 

 chroman or coumaran. This hypothesis of a heterocyclic ring structure 

 was justified by the results of an oxidation reaction with chromic acid 

 (9). When 4.3 g. of a-tocopherol was dissolved in glacial acetic acid 

 and oxidized with chromic acid, dimethylmaleic anhydride (IV) and 



/Cf /CH2 



CHa— C \ / ^CHa 



II o o=c I 



CHa— G / \ C— CieH 



33 



(IV) (V) 



a lactone, C21H40O2, were isolated. Structure V was proposed for 

 the lactone after a study of its properties and after a study of the 

 oxidation of the acetate of a-tocophcrol obtained from 25 g. of a- 



95 



