856 X. THE VITAMIN K GROUP 



1 ,4-naphthohydroqiiinone diphosphate, no such steric hindrance results, 

 and hydrolysis of the ester can proceed at an augmented rate. 



The organic ethers are very highly active, with the exception of the 2- 

 methyl-l,4-naphthohydroquinone dimesitoate, which is only slightly ef- 

 fective. Since this is hydrolyzable only with difficulty, because of steric 

 hindrance, it has been suggested by Fieser, Tishler, and Sampson^^ that 

 this offers support for the hypothesis that acylated naphthohydroquinones 

 undergo hydrolysis in the organism, and exert an antihemorrhagic effect by 

 functioning as the liberated hydroquinone. 



The ethers might be expected to be sufficiently resistant to breakdown so 

 that they would function much less efficiently as vitamin-K-like compounds 

 than the esters. However, they were found to be active in surprisingly 

 small amounts; this fact led Ansbacher, Fernholz, and Dolliver*^ to the 

 conclusion that in general the hydroquinone derivatives function as such 

 rather than as components of the hydroquinone-quinone oxidation-reduc- 

 tion system. Another possibility is that the methylnaphthohydroquinone 

 diethers may be readily converted to the corresponding quinones. Such a 

 reaction has been demonstrated in vitro with methylnaphthohydroquinone 

 dimethyl ether, which yielded methylnaphthoquinone on oxidation with 

 chromic acid.^'' Whether such a transformation can be effected in vivo has 

 not as yet been demonstrated. 



{8) Biological Activity of Hydrides of Vitamin K and of Methylnaphtho- 



quinones 



Partial hydrogenation in the cyclic portion of vitamin Ki, or in the 

 methylnaphthoquinone, may take place without a very great decrease in 



TABLE 10 



Antihemorrhagic Activity of Hydrides of Vitamin Ki and 



Methylnaphthoquinone" 



Efifective dose, 

 Compound Mg. 



5,8-Dihydrovitainin Ki*"'" 4 



i3,7,5,6,7,8-Hexahydro vitamin Ki*'^ 1000 (very slight) 

 2-Methyl-5,8-dihydro-l,4-naphthohydroquinone'' 6 



2-Methyl-5,8,9,10-tetrahydro-l,4-naphthoquinone'' 8 



2-Methyl-5,6,7,8-tetrahydro-l,4-naphthoquinone'' 500 



« L. F. Fieser, M. Tishler, and W. L. Sampson, J. Biol. Chem., 137, 659-692 (1941). 



* L F. Fieser, M. Tishler, and W. L. Sampson, J. Am. Chem. Soc, 62, 996 (1940). 



"= L. F. Fieser, M. Tishler, and N. L. Wendler, J. Am. Chem. Soc, 62, 2861-2866 

 (1940) 



<* M.' Tishler, L. F. Fieser, and N. L. Wendler, J. Am. Chem. Soc, 62, 2866-2871 

 (1940). 



M M. Tishler, L. F. Fieser, and W. L. Sampson, J. Am. Chem. Soc, 62, 1881-1882 

 (1940). 



