CHEMICAL STRUCTURE AND BIOLOGICAL ACTIVITY 825 



The only coumarone which has been studied is 2,4,6,7-tetraraethyl-5-hy- 

 droxycoumarone. It is devoid of vitamin E action."* 



H CH, 



HC» C ;CH, HOC C CH 



I II I I II II 



\ \ \''^ 



H CH, 



Coiunaran 2,4,6,7-Tetramethyl- 



5-hydroxycoumarone 



(5) Phenols 



Although phenol and most of its derivatives fail to possess vitamin E 

 activity, several substituted phenols have given positive results. This is 

 true of o-allylphenol, which is a possible intermediate in the synthesis of 

 chroman. Although it is inactive in 25-mg. doses, it is effective when ad- 

 ministered in the amount of 50 mg."^ Di-o-hexenylphenol and p-amino-o- 

 allylphenol"* are also active when fed in relatively large doses. 



<pH 



h/^ 



CCH,CH=CH, 



, :l 



HC. CH 



H 



0-AUyl- 

 phenol 



In spite of the fact that o-allylphenol is active, its isomer— o-propenyl- 

 phenol — is inactive. A large number of other phenols have also been 

 found to be devoid of activity. This list includes o- [a-methylallyl ]-, o- 

 hexenyl-, 2,3,5-trimethyl-, 6-allyl-, p-capryl-, p-tert-octyU, o-allyl p-car- 

 boxy-, and o-allyl-p-carbethoxy-phenols,"^ as well as two o-phenols with 

 •the following side chains: 



— CH(o-C6H40H)-CH2-C(OH):(n-C4H9)2; — CH(o-C6H40H).CH:CH.C(OH):(C2H5)2 



Evans et al.^^^ found that phenylhexenyl ether, phenylcinnamyl ether, 

 and p-carboxyphenylallyl ether are also inactive. 



(6) Quinones 



Practically all the quinones which have been studied are ineffective. 

 However, the red o-quinone oxidation product of a-tocopherol is active in 

 doses of 12 mg., although it is inactive when given in the amount of 3 or 6 

 mg. daily."* 



