490 THE TOCOPHEROLS 



containing one or two ethyl groups in place of the methyP° (or of H in 

 5,7-tocol) and allyl and crotyl derivatives^^ were prepared, as well as com- 

 pounds containing synthetic phytol or fewer isoprene units in the side 

 chain .'^2 With pseudocumol as starting material and by the use of Grignard 

 reactions, a wide variety of derivatives can be made, containing a side 

 chain other than the phytyl group; with cetyl the product was called iso- 

 a-tocopherol7^ m 



Most of these compounds were tested for their physiological action by 

 the method of rat assay (see below). Even with the earlier and less precise 

 procedures, certain general conclusions were readily apparent and are still 

 valid. If the activity of natural ^-tocopherol is set at 100, that of natural 

 iS-tocopherol is 40, and that of 7-tocopherol is 8 (or less).'^^' '^^ Figures for 

 the synthetic products were reported^^ as 100:25: 19. 5-Tocopherol has only 

 1 % of the biological activity of the a.^^ By contrast, nuclear dealkylation 

 increases antioxygenic action^^' '''' and resistance to atmospheric oxidation,^^ 

 but if the distinction between antioxygenic activity, as usually measured 

 in accelerated tests at 70° to 100°, and antioxidant potency measured at 

 body temperature is valid, the latter and the biological activity run paral- 

 lel.''^ Optical activity (residing in carbon 2) is very slight, but the potencies 

 of the synthetic dl compounds (a and /3) were found to be two-thirds and 

 one-half, respectively, of those of the natural.''^ For the cure of nutritional 

 muscular dystrophy in rabbits, the ratios of potency for the a, 13, and 7 

 varieties were reported as 100:30:20, and the synthetic a and 7 about 90 

 and 30 % of the natural .^o 



The biopotency of the esters is equal to that of the free alcohols, or even 

 slightly greater, because the esters are not autoxidizable. The use of the 

 crystalline succinate was suggested as a vitamin E standard^^ in place of 



70 P. Karrer and O. Hoffmann, Helv. Chim. Acta 22, 654 (1939); 23, 1126 (1940); P. 



Karrer, H. Fritzsche, and R. Escher, ibid. 22, 661 (1939); P. Karrer and R. 



Schlapfer, ibid. 24, 298 (1941). 

 '1 P. Karrer, R. Escher, H. Fritzsche, H. Keller, E. H. Ringier, and H. Salomon, 



Helv. Chim. Acta 21, 939 (1938). 

 '2 P. Karrer and K. A. Jensen, Helv. Chim. Acta 21, 1622 (1938); P. Karrer and H. 



Fritzsche, ibid. 22, 260 (1939); P. Karrer and B. H. Ringier, ibid. 22, 610 (1939); 



P. Karrer, H. Koenig, B. H. Ringier and H. Salomon, ibid. 22, 1139 (1939); P. 



Kerrer and K. S. Yap, ibid. 23, 581 (1940). 

 " W. John, P. Giinther, and F. H. Rathmann, Z. physiol. Chern. 268, 104 (1941). 

 7* M. Joffe and P. L. Harris, /. Am. Chem. Soc. 65, 925 (1943). 



'^ L. Weisler, J. G. Baxter, and M. I. Ludwig, J. Am. Chem. Soc. 67, 1230 (1945). , 

 '6 H. Gottlieb, F. W. Quackenbush, and H. Steenbock, J. Nutrition 25, 433 (1943). ! 

 " C. Golumbic, /. Am. Chem. Soc. 63, 1142 (1941). 

 '8 E. L. Hove and Z. Hove, /. Biol. Chem. 156, 623 (1944). 



79 P. L. Harris, J. L. Jensen, M. Joffe, and K. E. Mason, J. Biol. Chon . 156, 491 (1944). 

 so E. L. Hove and P. L. Harris, /. Nutrition 33, 95 (1947). 



