II. CHEMISTRY 397 



form/^' *^ The diesters of this compound were also found to be active. The 

 bisulfite addition product of methylnaphthoquinone is water soluble and 

 highly active. ^^ A number of other compounds easily convertible to methyl- 

 naphthoquinone in metabolism probably owe their activity to such con- 

 version. Among these are l-hydroxy-2-methyl-, l-hydroxy-3-methyl-, and 

 l-amino-2-methylnaphthalene, 3-methyl-l-tetralone, and 2-methyl-l-tetra- 

 lone.^ The water-soluble compounds, 4-amino-2-methyl-l-naphthol hydro- 

 chloride and 4-amino-3-methyl-l-naphthol hydrochloride were found to be 

 approximately as potent as vitamin Ki.^^ Using the Craven's ethyl cyano- 

 acetate color reaction for quinones as a quantitative method, Richert^® 

 demonstrated the biological conversion of 4-amino-2-methyl-l-naphthol, 

 2-methyl-l,4-naphthohydroquinone diphosphate, and 2-methyl tetralone 

 to methylnaphthoquinone. The excretion of the latter in the urine of the 

 rabbit and chicken increased significantly when any of the first three were 

 fed. 



Several naturally occurring 3-hydroxynaphthoquinones having a larger 

 side chain in place of the methyl group of phthiocol were reported to show 

 some activity," but this could not be confirmed.*^- " Among these were 

 lapachol, hydrolapachol, and lomatiol. l-Methyl-2-hydroxy-, 2-methyl-3- 

 hydroxy-, and l-methyl-4-hydroxynaphthalenes were not appreciably ac- 

 tive.^* A discussion of the relation of structure to activity has been pub- 

 lished by Fieser et al.^^ 



In view of the results with the above-mentioned compounds it was sur- 

 prising that the 2-methyl- 1,4-naphthohydroquinone diphosphoric acid es- 

 ter was found to be more active on a molecular basis than the parent methyl- 

 naphthoquinone.^^- *^' ^^ The corresponding disulfate, however, was 

 markedly less potent.^-' ^^ These differences may be related to differences 

 in speed of absorption or of regeneration of the methylnaphthoquinone. 

 The interest in these and other water-soluble forms of vitamin K hinges 

 on their greater convenience for injection and their independence on bile 

 or bile salts for absorption from the alimentary tract. 



Comparative five-day assays of vitamins Ki and K2 have indicated that 

 the relative potencies are in the ratio of 1.25:1.^^ This is the approximate 

 ratio of the amount of the active methylnaphthoquinone nucleus contained 

 in each. Assays by shorter procedures have indicated a potency ratio of 



63 B. R. Baker, T. H. Davies, L. McElroy, and G. H. Carlson, /. A^n. Chevi. Soc. 64, 



1096 (1942). 

 " M. Tishler, L. F. Fieser, and W. L. Sampson, /. At7i. Chem. Soc. 62, 1881 (1940). 

 " D. Richert, S. A. Tliayer, R. W. McKee, S. B. Binkley, and E. A. Doisy, Proc. Soc. 



Exptl. Biol. Med. 44, 601 (1940). 

 " D. A. Richert, /. Biol. Chem. 154, 1 (1944). 



" L. F. Fieser, W. P. Campbell, and E. M. Fry, /. Am. Chem. Soc. 61, 2206 (1939). 

 68 R. H. K. Foster, J. Lee, and U. V. Solmssen, /. Am. Chem. Soc. 62, 453 (1940). 



