850 X. THE VITAMIN K GROUP 



OH 



II 



'K f"* 



c ■ c " ? 



Hcr \ c \h Hcr \ c-ch,ch=cch,ch,ch=c-ch5 



I II II I I II II J 



H II I H 



OH 



XK XX 



(4) E'^ecf o/ Replacement of Naphthoquinones with Carhethoxy or Hydroxy 



Groups 



Practically all of the hydroxynaphthoquinones are inactive except when 

 a methyl group is retained on the 2-position. Even in these cases, the 

 effectiveness of such compounds in relieving hemorrhagic tendencies due to 

 the lack of vitamin Ki is greatly depressed. The relative biological activi- 

 ties of these various hydroxynaphthoquinones are summarized in Table 6. 



TABLE 6 

 Biological Activity of Carbethoxy- and Hydroxynaphthoquinones 



Effective dose, 

 Compound Mg- 



2-Methyl-3-carbethoxy-l,4-naphthohydroquinone" 25 



2-Methyl-5-hydroxy-l,4-naphthoquinone (plumbagin)* 400 



2-Methyl-3-hydroxy-l,4-naphthoquinone (phthiocol)'= 500 



2-/3-Heptenyl-3-hydroxy-l,4-naphthoqumone'' Inactive at 1000 



2-Farnesyl-3-hydroxy-l,4-naphthoquinone'' Inactive at 1000 



2-Methyl-3-(7-hydroxydihydrophytyl)-l,4-naphthohydroqui- Inactive at 1000 



none* 

 5-Hydroxy-l,4-naphthoquinone (juglone)^ Inactive at 1000, 



feebly positive at 10,000 

 2-Hydroxy-l,4-naphthoquinone (lawsoney." Inactive at 1000, 



active at 10,000 

 2-Hydroxyl-3-dimethyl-allyl-l,4-naphthoquinone (lapachoiy Inactive at 1000, 



active at 5000 

 Hydroquinone diacetate'' Inactive at 1000 



» C. F. Koelsch and D. J. Byers, J. Am. Chem. Soc, 62, 560-562 (1940). 



* L. F. Fieser and J. T. Dunn, ./. Am. Chem. Soc, 58, 572-575 (1936). 

 « H. J. Almquist and A. A. Klose, J. Am. Chem. Soc, 61, 1611 (1939). 



■' L. F. Fieser, M. Tishler, and VV. L. Sampson, J. Biol. Chem., 137, 659-692 (1941). 



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

 (1940). 



^ R. Kuhn, K. Wallenfels, F. Weygand, T. Moll, and L. Hepding, Naturwissenschaften, 

 27, 518-519 (1939). 



" H. Dam, J. Glavind, and P. Karrer, Helv. Chim. Ada, 23, 224-233 (1940). 



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

 (1940). 



Phthiocol (XXI) was the first simple compound which was demon- 

 strated to have an antihemorrhagic effect.*^ Although phthiocoP^ c^n 

 condense with the reduced form of phytol to give a low yield of vitamin 

 Ki,^^ the reaction does not explain the activity of this compound, since its 



" H. J. Almquist and A. A. Klose, J. Am. Chem. Soc, 61, 1611 (1939). 



