CHEMICAL STRUCTURE AND BIOLOGICAL ACTIVITY 849 



given in Table 5. The positions of the substituted groups can be deduced 

 from the numbering of 1,4-naphthoquinone. 



/^K /*\ 



HCs C 3CH 



I I! II 



H II 







1 ,4-Naphthoquinone 



TABLE 5 



Biological Activity of Highly Alkylated Derivatives of 1,4-Naphthoquinones 



AS Antihemorrhagic Agents" 



Compound 



Effective dose, 



2,5-Dimethyl-l,4-iiaphthoquinone^ 500 



2,6-Dimethyl-l,4-naphthoqumone'' Inactive at 1000 

 2,7-Dimethyl-l ,4-naphthoquinone« 1000 



2,8-Dimethyl-l,4-naphthoqumone'' 500 



6, 7-Dimethyl- 1,4-naphthoquinone'*'^ Inactive at 1000 



2,6-Dimethvl-3-phvtvl-l,4-naphthoquinone-'' Inactive at 1000 

 2,3-Diallyl-"l ,4-naphthoquinone''-« 1000 



2-Ethyl-3-phytyl-l ,4-naphthoquinone^ 1000 



1 ,2,4-Trihydrox3'anthraquinone» 100 



l,l-Dimethyl-3-/e/-<-butyl-l,4-dihydroanthraquinone'' Inactive at 1000 



2-(6-Methyi-7-pentenyl)-l,4-dihydroanthraquinone'' Inactive at 1000 



" H. R. Rosenberg, Chemistry and Physiology of the Vitamins, Interscience, New York, 

 1945, p. 497. 



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

 (1940). 



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



<* L. F. Fieser, W. P. Campbell, and E. M. Fry, /. Am. Chem. Soc, 61, 2206-2218 

 (1939). 



« L. F. Fieser, D. M. Bovven, W. P. Campbell, E. .M. Frv, and M. D. Gates, J. Am. 

 Chem. Soc., 61, 1926-1927 (1939). 



/ L. F. Fieser, /. Am. Chem. Soc, 61, 3467-3475 (1939). 



» G. J. Martin and C. F. Lischer, /. Biol. Chem., 137, 169-171 (1941). 



'' L. F. Fieser and C. W. Wieghard, /. Am. Chem. Soc, 62, 153-155 (1940). 



The introduction of a second meth}'! group into positions 5 or 8 lowers the 

 potency to 1/1500 as compared with that of menadione; when the second 

 methyl group is on position 7, the product has only 1/3000 the potency of 

 2-methyl-l,4-naphthoquinone. Finally, when the second methyl group is 

 placed in position 6, the resulting product is devoid of activity at 1000 jug- 

 The ethyl analogue of vitamin Ki (2-ethyl-3-phytyl-l,4-naphthoquinone) 

 has only 1/1000 the biological activity of vitamin Ki. It is interesting 

 that 1,2,4-trihydroanthraquinone (XIX) is fairly potent, while 2-(5-methyl- 

 7-pentenyl)-l,4-dihydroanthraquinone (XX) is completely inactive at a 

 dose of 1000 Mg. 



