848 X. THE VITAMIN K GROUP 



HC C CH 



H II 







2-R-l ,4-naphthoquinone 



The most striking phenomenon evident from Table 4 is the profound im- 

 portance of the methyl group in position 2. 2-Methyl-l,4-naphthoquinone 

 occupies a unique position, since it is 170 times as potent as the next most 

 active member of the series. Whereas menadione is biologically effective 

 in doses of 0.3 jug-, the next two higher homologues, namely, 2-ethyl- and 2- 

 n-propyl-l,4-naphthoquinone, are inactive in doses of 1000 jug- The latter 

 finding has been confirmed by Fernholz et al.,''^ as well as by Sjogren.*^ 

 Another interesting result is the fact that the order of activity for the hy- 

 drocarbon side chains on position 3 in 2-methyl-l,4-naphthoquinone is the 

 same as it is when the methyl group is absent. Thus, phytyl > farnesyl > 

 dihydrophytyl > geranyl, but these compounds are only 2, 1, 1.4, and 2.5%, 

 respectively, as active as are the corresponding 2-methyl-3-R-l,4-naph- 

 thoquinones. 



Fieser^^ suggested that the commanding position occupied by menadione 

 may not be due to the functioning of the compound as such but rather to its 

 rapid transformation in the body to a quinone of the vitamin K type. 

 Since the simple reduced quinone readily condenses with phytol, farnesol, 

 and geraniol in vitro, it would presumably also react in vivo with other (8- 

 unsaturated isoprenoid alcohols to yield antihemorrhagic compounds. It 

 is altogether possible that such an alcohol might be derived from the break- 

 down of the aliphatic side chain of vitamin A. Menadione would therefore 

 give rise to 2.6 parts of vitamin Ki or 3.4 parts of vitamin K2, if such syn- 

 theses were quantitative. These relationships are approximately those 

 which have actually been found. 



(3) Effect of High Alkylation on Activity of 1 ,4-Naphfhoquinones 



When several alkyl groups are substituted on the 1,4-naphthoquinones, 

 profound changes may result, even if the methyl group is still attached to 

 position 2. Thus, when the second methyl group is at positions 5,6, 7, or 8, 

 the resulting compound has been found to possess only slight activity, or to 

 be completely devoid of any biopotency when fed in an amount as high as 

 1000 fig. A summary of the data on such highly alkylated compounds is 



81 B. Sjogren, Z. physiol. Chem., 262, I-III (1939). 



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



