796 IX. THE VITAMIN E GROTTP 



half to one-third of that of a-tocopherol. 5-Tocopherol represents the last 

 member of the series to be added to the group of vitamins E^^; it has been 

 found to possess the least antisterility effect and the greatest antioxidant 

 activity of the group. 



The work of Evans et al.^'^ was confirmed in 1937 by Todd, Bergel, Wald- 

 mann, and Work.^^-^^ According to later reports,^^ these workers prepared 

 a new allophanate which they designated as jS-tocopheryl allophanate. It 

 was found to melt at 143.5-144.5°C. Apparently it is the same allo- 

 phanate which was separated in impure form by Evans et al.,^- melting at 

 136-138°C., which was subsequently further purified by acetone recrystal- 

 lization to yield a product with a melting point in agreement (144-146°C.)^* 

 with the preparation of the latter workers. 



The structural relationships of the tocopherols were worked out by 

 Fernholz.^'-^" The tocopherols were shown to have the chroman ring. 

 a-Tocopherol contains three methyl groups, and the structure was found 

 to agree with the empirical formula C29H50O2, suggested by Evans and co- 

 workers.^'^ The /3- and 7-forms have one less methyl group, which is in line 

 with the formula of C28H48O2, while 5-tocopherol has only one methyl group. 



The chemical synthesis of rf^a-tocopherol was first accomplished by 

 Karrer, Fritzsche, Ringier, and Salomon in 1938,^^"^' and was later con- 

 firmed by Smith, Ungnade, and Prichard.^* Two of the naturally occurring 

 tocopherols, a and 7, have recently been prepared in crystalline form.*^'*^ 

 Natural /3-tocopherol could not be crystallized under similar treatment; 

 /3-tocopherol azobenzene carboxylate was the only ester of /3-tocopherol — 

 with the exception of the allophanate — ^which could be crystallized. 



Several extensive reviews on the physiology of vitamin E include those of 

 Evans, ^^ Mattill,''^ and Mason,^^ while Smith^'' covered the chemical aspects 

 of the field. 



^ M. Stern, C. D. Robeson, L. Weisler, and J. G. Baxter, /. Am. Chem. Soc, 69, 869- 

 874 (1947). 



36 A. R. Todd, F. Bergel, H. Waldmann, and T. S. Work, Nature, I40, 361-362 (1937). 



37 A. R. Todd, F. Bergel, H. Waldmann, and T. S. Work, Biochern. J., 31, 2247-2256 

 (1937). 



38 A. R. Todd, F. Bergel, and T. S. Work, Biochern. J., 31, 2257-2263 (1937). 



39 E. Fernholz, J. Am. Chem. Soc, 59, 1154-1155 (1937). 

 «> E. Fernholz, /. Am. Chem. Soc, 60, 700-705 (1938). 



" P. Karrer, H. Fritzsche, B. H. Ringier, and H. Salomon, Nature, I4I, 1057 (1938). 



^2 P. Karrer, H. Fritzsche, B. H. Ringier, and H. Salomon, Helv. Chim. Acta, 21, 520- 

 525 (1938). 



" P. Karrer, H. Fritzsche, B. H. Ringier, and H. Salomon, Helv. Chim. Acta, 21, 820- 

 825 (1938). 



« L. I. Smith, H. E. Ungnade, and W. W. Prichard, Science, 88, 37-38 (1938). 



*^ J. G. Baxter, C. D. Robeson, J. D. Taylor, and R. W. Lehman, /. Am. Chem. Soc, 

 65, 918-924 (1943). 



"6 C. D. Robeson, J. Am. Chem. Soc, 65, 1660 (1943). 



« H. M. Evans, J. Am. Med. Assoc, 99, 469^76 (1932). 



"8 H. A. Mattill, J. Am. Med. Assoc, 110, 1831-1837 (1938). 



« K. E. Mason, Vitamins and Hormones, 2, 107-153 (1944). 



" L. I. Smith, Chem. Revs., 27, 287-329 (1940). 



