CHEMICAL STRUCTUKE AND BIOLOGICAL ACTIVITY 823 



CH, 

 HOC C CH, 



I i I 



H3CC C C-(CH,)„CH3 



\ \h3 



CHj 



2-Dodecyl-2,5,7,8-tetrainethyl-&-oxychroman 



Karrer and Stahelin^'*" have recently prepared two homologues of a- 

 tocopherol in which the methyl group on position 2 is replaced by an ethyl 

 or propyl side chain. The acetates of both of these compounds have been 

 found to be active in 10-mg. but not in 5-mg. dailj^ doses. 



The natural tocopherols behave in an inverse manner as antioxidants and 

 as antisterility agents. ^^-^^^ Thus, a-tocopherol is the most potent and 

 5-tocopherol the least effecti\'e in vitamin E activit3^ On the other hand, 

 5-tocopheroi is the member which is most efficient as an antioxidant, fol- 

 lowed in order by y-, )3-, and a-tocopherol. 



(S) Chromans and Chromene Derivatives 



Chroman itself has been shown to possess some biological potency.^'" 

 This is tme also for 2,2-diethyl- and 2,2-di-n-butylchroman.^^* On the 

 other hand, 2,2-dimethyl- and 2,2-dipropylchromans have no activity. ^^^ 



H H, 



C C 



/^\/*\ 



HC6 C sCH, 



I i| I 



C 



H 



Chroman 



This alteration in activity is a verj^ curious one, and may be related to 

 variations in end products resulting from the oxidation of the hydrocarbon 

 chains in position 2. The only other chroman reported as active is 2,5,7,8- 

 tetramethjdchroman.^^* Evans et al.^^^ proved that 2,2,3-trimethyl-, 2- 

 methyl-4-ethyl-, and 2,2,5,7-tetramethylchromans are all inactive. 



Although 6-hydroxychroman is inactive, two of its derivatives, nameh', 

 2,2,5,7,8-pentamethyl-^^^ and 2,5,7,8-tetramethyl-2-dodecyl-6-hydroxy- 

 chroman,^^^ have been found to be active when given in 100-mg. and 60-mg 

 daily doses, respectively. Other compounds studied which were found to 

 be mactive included 2,5,7,8-tetramethyl-,i3<'-i37.i39 2,3,5,7,8-pentamethyl-,i39 

 and 2,5,7,8-tetramethyl-2-isohexyl-6-hydroxychroman.^^* 



Three chromene derivatives have been reported as ineffective.^^* These 

 are 2,2-dimethyl-, 2,2-diethyl-, and 2,2-di-?i-butylchromenes. 



"0 P. Karrer and M. Stahelin, Heir. Chim. Acta, 28, 438-443 (1945). 

 "1 W. Johu, Angcw. Chem., 52, 413-419 (1939). 



