822 IX. THE VITAMIX E GROUP 



at a 25-mg. dosage and a vitamin K effect when given in amounts of 300 to 

 600 Mg.'^' 



CHj 



HOC C CH, CH3 CH, CH, 



I il l_ 



/C C C L,,,3.,,..,,,3. 



HC C CH, 



HC CH 



Naphthotocopherol 



Although the replacement of the methyl groups attached to the chroman 

 ring with ethyl radicals profoundly alters the physiological activity, just as 

 does the complete removal of such side groups, it is possible to introduce a 

 double bond into the chroman ring without exerting a marked effect upon 

 biopotency. Thus, Karrer, Legler, and Schwab ^^^ found that d/-3,4- 

 dehydro-a-tocopherol is active in amounts of about 6 mg. 



CH, 



C CH 



HOC 'C ^CH CH, CH, CH3 



li I I III 



HjCC C C— (CHjljCHlCHjljCHICHjJjCHCHj 



C'''^ CHj 



CH3 



dZ-3,4-Dehydro-a-tocopherol 



The side chain on carbon 2 probably has the most specific requirements of 

 any part of the molecule. When this is shortened by one isoprene unit of 5 

 carbons, — CH2-CH2-CH(CH3)CH3, the resulting compound is inactive 

 when administered in 20-mg. doses; the effect of larger quantities has not 

 been tested. ^^^ When the side chain is shortened by 2 isoprene units, no 

 biological activity can be detected in doses as high as 40 mg. daily. ^^^ The 

 introduction of a double bond in the long side chain likewise causes a loss of 

 physiological activity. ^^^ When the side chain is completely removed, or is 

 replaced by a methyl group, the resulting compound is devoid of any 

 antisterility effect^^^ when fed in doses of 30 mg. However, John and co- 

 workers^^* have prepared 2-dodecyl-2,5,7,8-tetramethyl-6-oxychroman, 

 which Rosenberg^^ states is active when fed in 60-mg. doses. 



135 M. Tishler, L. F. Fieser, and N. L. Wendler, /. Am. Chem. Soc, 62, 1982-1991 

 (1940). 



136 P. Karrer, R. G. Legler, and G. Schwab, Helv. Chim. Acta, 23, 1132-1137 (1940). 

 1" P. Karrer and K. A. Jensen, Helv. Chim. Acta, 21, 1622-1624 (1940). 



138 p. Karrer and K. S. Yap, Helv. Chim. Acta, 23, 581-584 (1940). 

 "9 W. John, P. Giinther, and M. Schmeil, Ber., 71, 2637-2649 (1938). 



