CHEMICAL STRUCTURE AND BIOLOGICAL ACTIVITY 853 



potency, below its unoxidized parent substance. It is believed that the 

 transformation to the corresponding unoxidized hydroquinone may not 

 proceed as efficiently as in the case of the vitamin Ki oxide. It is also 

 possible that the oxide of the 2-alkyl-l,4-naphthoquinones in which the 3- 

 position is not protected may form the corresponding 3-hydroxy compound 

 in vivo. Thus, the oxide of 2-methyl-l,4-naphthoquinone is converted by 

 the action of sulfuric acid at a low temperature into phthiocol.^^ Further- 

 more, under the influence of alkali, the 2-methyl oxide may isomerize partly 

 into phthiocol and partly into lawsone, with the loss of a methyl group. ^^ 

 The 2-alkyl-l,4-naphthoquinone oxides which have side chains longer 

 than those of methyl on position 2 do not suffer such a marked decrease in 

 potency as is the case with 2-methyl-l,4-naphthoquinone oxide. Fieser 

 et al."^'^ explain this paradox as due to the fact that the large isoprenoid 

 groups manifest a protective influence in preventing hydrolytic cleavage of 

 the oxide linkage. 



{6) Biological Activity of Other Miscellaneous Quinones 



Although most of the quinones other than the naphthoquinones were 

 shown to be inactive at levels of 1000 idg., two members in this series do re- 

 spond in a positive manner. These include 2-methyl-2-phytyl-2,3-dihy- 

 dro-l,4-naphthoquinone (XXV) and naphthotocopherol (XXVI). 



CH, 



H ^ H I I 



/\ /^\ /\ /\ /^^' 



HC- C CH, HO- V -C 



I 'I I ^3 I :| I 



HC, b ,C-CHXH=CCH,C,5H3, HC, b .CCH. 



VV\h vv 



H II ' HI 



OH 



Table 8 lists some of the miscellaneous quinones tested, and the level at 

 which the positively reacting members responded. 



The high potency of 2-methyl-2-phytyl-2,3-dihydro-l,4-naphthoquinone 

 is difficult to explain, although it is isomeric with vitamin Ki hydroquinone. 

 However, the Fieser group^^-'^^'™ have shown that it can be converted to 

 vitamin Ki by pyrolysis and oxidation to the extent of 1 to 2%. Possibly, 

 some such avenue of transformation is also available in vivo. 



Naphthotocopherol occupies a unique position among the vitamins in 

 that it has a dual effect. It can act both as an antisterility agent and as an 

 antihemorrhagic vitamin. It is conceivable that the latter activity results 



87 L. F. Fieser, /. Biol. Chcm., 133, 391-396 (1940). 



