854 X. THE VITAMIN K GROUP 



TABLE 8 

 Antihemorrhagic Activity of Some Miscellaneous Quinonbs" 



Compound 



Effective dose, 



2-Methyl-2-phytyl-2,3-dihydro-l,4-nyphthoquitioiie'''' 50 



Naphtliotocophcrol''''' 500 



Duroquinone" Inactive at 1000 



a-Tocopherylquinone" " " " 



9-Methylperinaphthenone-7'' " " " 



2,3,5-Trimethyl-l,4-benzoquinone" " " " 



2,3,5-Trimethyl-6-phytyl-l,4-benzoquinone'''''''' " " " 



" Adapted from L. F. Fieser, M. Tishler, and W. L. Sampson, /. Biol. Chem., 137, 

 659-692(1941), p. 677. 



^ L. F. Fieser, M. Tishler, and W. L. Sampson, J. Am. Chem. Soc, 62, 996, 1628-1629 

 (1940). 



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

 (1940). 



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

 (1940). 



• L. F. Fieser, M. Tishler, and N. L. Wendler, /. Am. Chem. Soc, 62, 2861-2866 (1940). 



from the breakdown of the chroman ring, since jS,7-dihydrovitamin Ki 

 would result. This latter compound is effective when administered at a 

 level of 8 jug. 



(7) Biological Activity of N ayJithohydroquinone Esters and Ethers 



The naphthohydroquinones can be reversibly changed to the corre- 

 sponding naphthoquinones in the body. Presumably, the formation of 

 such an oxidation-reduction system may explain their physiological be- 

 havior in the animal. Although the naphthohydroquinones differ little in 

 solubility from the corresponding quinones, they do form inorganic esters 

 which readily dissolve in water. Such products arc widely used for paren- 

 teral therapy. A number of sulfate and phosphate esters have been syn- 

 thesized by Fieser and Fry,^^ who also investigated their biological activity. 



The investigation of organic esters has been prompted by the demon- 

 stration by Binkley et al.*^ that the crystalline hydroquinone diacetates of 

 vitamins Ki and Ka have about 50% of the potency which is exhibited by 

 the corresponding quinones. The dibenzoate and dimethyl ethers have 

 likewise been studied; Ansbacher, Fernholz, and Dolliver^^ were the first to 

 report on these ethers. The results of these and of other investigators are 

 summarized in Table 9. 



88 L. F. Fieser and E. M. Fry, /. Am. Chem. Sac, 62, 228-229 (1940). 

 8' S. Ansbacher, E. Fernholz, and M. A. Dollivcr, /. Am. Chem. Soc, 62, 155-158 

 (1940). 



