858 X. THE VITAMIN K GROUP 



to the fact that they cannot be readily dehydrogenated in the same manner 

 as can the compounds which possess an activating double bond. It is only 

 when such compounds can be transformed to the naphthoquinones that 

 they are able to exert activity as antihemorrhagic agents. 



(9) Biological Activity of Methylnaphthols, of Methyltetralones, and of Some 



Related Compounds 



Apparently it is not always necessary that a substance have the quiiione 

 or hydroquinone structure in order to exert a vitamin K effect. Fieser and 

 his co-workers have demonstrated high activity on the part of certain naph- 

 thols and tetralones.^--^*' A summary of their findings, as well as of the re- 

 sults of the Doisy group^^-^^ and others^^, on some related amines is given in 

 Table 11. 



Although 2-methyl-l-naphthol (XXVII) and 3-methyl-l-naphthol 

 (XXVIII) are extremely potent antihemorrhagic agents, the corresponding 

 4-methylnaphthol is entirely ineffective. Moreover, the two methyl-/3- 

 naphthols tested (where the hydroxyl is on position 2) are entirely inactive. 

 The only methylnaphthols which exhibit biological activity are those two 

 which are directly convertible to 2-methyl-l,4-naphthoquinone; the three 

 which cannot yield such a product are completely inactive. Fieser et al.^^ 

 believe that the animal possesses an extremely efficient hydroxylation 

 mechanism which acts on the carbon in para position to the original hy- 

 droxyl group. 



H H H H 



HC C CH HC' C -CCH, 



I il I I 11 I 



HC^ C .CCH, HC C XH 



\ \^ C C^ 



HI HI 



OH OH 



The methyltetralones also show activity comparable to that of the meth- 

 ylnaphthol. It is believed that 2-methyl-l-tetralone (XXIX) and 3- 

 methyl-1-tetralone (XXX) can be effectively aromatized in the body to the 

 corresponding naphthols. Their conversion to 2-methyl-l,4-naphthoqui- 

 nones would follow, as has been assumed for the naphthols. 



92 E. A. Doisv, D. W. MacCorquodale, S. A. Thayer, S. B. Binkley, and R. W. McKee, 

 Science, 90, 407 (1939). 



93 D. Richtert, S. A. Thayer, R. W. McKee, S. B. Binkley, and E. A. Doisy, Proc. 

 Soc. Exptl. Biol. Med., 44, 601-604 (1940). 



9^ H. J. Almquist and A. A. Klose, Proc. Soc. Exptl. Biol. Med., 45, 55-59 (1940). 



