820 IX. THE VITAMIN E GROUP 



sterile female rats for the full 21 days of gestation, brings about the birth of 

 at least one living young in 50% of the animals. This corresponds to about 

 2 to 3 mg. of a-tocopherol. Another standard is the Pacini-Linn Unit, 

 which equals about one-tenth of the Rat Unit^^; the Bromskov RatUnit^^^ 

 is the amount of vitamin E which, when administered once during the first 

 8 days of pregnancy, prevents resorption of the fetuses. These standards 

 apply to vitamin E only in relation to its biological activity, and are not 

 used in considering its antioxidant behavior. 



7. Chemical Structure in Relationship to Biological Activity of 

 Vitamins E and of Yitamin-E-Like Compounds 



Something over 130 compounds have been studied for their vitamin E 

 activity."* Of these about 40 have shown some biological potency, al- 

 though none compares with the tocopherols in this respect. Whereas dif- 

 ferent tocopherols are active in amounts varying from 3 to 20 mg., from 50 

 to 100 mg. of the other substances showing vitamin E activity are required 

 to produce a positive effect. In several cases, the amount in which the 

 compound must be fed to produce biological activity approaches the level at 

 which toxicity develops. 



Any change in the groups on the aromatic nucleus or on the long ali- 

 phatic side chain markedly alters the vitamin E activity. It is also neces- 

 sary that the hydroxyl group on the benzene ring be in para position to the 

 oxygen in the bridge. The effectiveness can be masked by any of several 

 carboxylic esters without marked reduction in activity,"^-'™ although the 

 allophanates^^ and the ethers are completely without any antisterility 

 effect.60 



(1) Tocopherols 



a-Tocopherol possesses the greatest potency of any of the natural or 

 synthetic products which have a vitamin E activity. It is effective when 

 administered in doses of 2 to 3 mg. per day. Although the f//-mixture of a- 

 tocopherol has generally been considered to have a biological activity 

 identical with that of natural c^-a-tocopherol,^^-^^-^-^ recent reports of Harris 

 and his collaborators indicate that the d-form has considerably greater 

 potency than the synthetic ^/-mixture (1.36:1).^--"^^^ 



11' C. Bromskov, Arch, exptl. Path. Pharmakol, 190, 627-647 (1938). 



"8 H. M. Evans, O. H. Emerson, G. A. Emerson, L. I. Smith, H. E. Unsnade, W. W. 

 Prichard, F. L. Austin, H. H. Hoehn, I. W. Opie, and S. Wawzonek, J. Org. Chem , 4, 

 376-388 (1939). 



11* V. Demole, O. Isler, B. H. Ringier, H. Salomon, and P. Karrer, Helv. Chim. Acta, 

 22, 65-68 (1939). 



120 O. Isler, Hch. Chim. Acta, 21, 1756-1759 (1938). 



121 P. Karrer and B. H. Ringier, Helv. Chim. Acta, 22, 610-616 (1939). 



122 P. L. Harris, J. L. Jensen, M. Joffe, and K. E. Mason, J. Biol. Chem., 156, 491-498 

 (1944). 



123 p. L. Harris and M. I. Ludwig, /. Biol. Chem., 179, 1111-1115 (1949). 



124 P. L. Harris and M. I. Ludwig, /. Biol. Chem.., 180, 611-614 (1949). 



