CUKMKAL STllUCTVIRE AND lUOLOfiK^AL ACTIVITY (S5rj 



TABLE 9 



axtihemorrhagic activity of some inorganic and organic esters and of some 

 Ethers of Naphthohydroquinone" 



Effective dose. 

 Compound /ig. 



Inorganic esters 



Sodium 2-methyl-l,4-naphthohydroquinone diphosphate''''^''' 0.5 



Sodium 2-methyl-l,4-naphthohydroquinone disulfate**-'' 2 



Vitamin Ki hydroquinone diphosphoric acid*" 25 



Sodium 2,3-dimethyl-l,4-naphthohydroquinone disulfate* Inactive at 500' 



Potassium vitamin Ki hydroquinone disulfate** Inactive at 500 



Organic esters 



Diacetate of 2-methyl-l,4-naphthohydroquinone-'^''' 1 



Dibenzoate of 2-methyl-l,4-naphthohydroquinone'''<' 1 



Dimesitoate of 2-methyl-l,4-naphthohydroquinone'''* 300 

 Vitamin Ki hydroquinone diacetate' 2 



Vitamin Ko hydroquinone diacetate' 3 . 2 



Ethers 



Monoethyl ether of 2-inethyl-l,4-naphthoh}'droquinone'= 1 



Dimethyl ether of 2-methyl-l,4-naphthohydroquinone'' 5 



Dibenzyl ether of 2-methyl-l,4-naphthohydroquinone/ 7 



" L. F. Fieser, M. Tishier, and W. L. Sampson, /. Biol. Chem., 137, 659-692 (1941). 



'' L. F. Fieser and E. M. Fry, /. .4m. Chem. Sec, 62, 228-229 (1940). 



"= R. H. K. Foster, J. Lee, and U. V. Solmssen, /. Ain. Chem. Soc, 62, 453-454 (1940). 



•^ S. Ansbacher, E. Fernholz, and M. A. DolHver, Proc. Soc. Exptl. Biol. Med., 43, 

 652-655 (1940). 



« Reported as active at 500 mS- by L. F. Fieser, et al, J. Biol. Chem., 137, 659-692 

 (1941). 



f L. F. Fieser, W. P. Campbell, E. M. Fry, and M. D. Gates, /. Am. Chem. Soc, 61, 

 2559, 3216-3223 (1939). 



" S. Ansbacher, H Fernholz, and M. Dolliver, /. Am. Chem. Soc., 62, 155-158 (1940). 



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

 (1940). 



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

 (1940). 



i S. B. Binklev, D. W. MacCorquodale, L. C. Cheney, S. A. Thayer, R. W. McKee, 

 and E. A. Doisy, J. Am. Chem. Soc, 61, 1612-1613 (1939). 



* M. Tishier, L. F. Fieser, and N. L. Wendler, J. Am. Chem. Soc, 62, 1982-1991 

 (1940). 



The most striking finding in regard to the naphthohydroquinones is the 

 fact that the diphosphate ester of the 2-meth3d derivative is active in a 

 O.o-pg. dose, which corresponds to 0.2 /ug- of the free 2-methyl-l,4-naph- 

 thoquinone. Since the minimum level at which the corresponding un- 

 esterified compound is effective is at 0.3 jug-, it is apparent that an in- 

 creased activity obtains. On the other hand, the diphosphoric acid ester 

 of vitamin Ki hydroquinone has only one-fiftieth of the activity of the free 

 vitamin. Since it is believed that the vitamin K effect is obtained only 

 following hydrolysis of the esters, the decreased potency of the vitamin Ki 

 diphosphoric acid ester would result from the difficulty of accomplishing 

 this hydrolysis, due to the hindrance of the bulky isoprenoid side chain. 

 Where only a methyl group is involved, as in the case of sodium 2-methyl- 



