CHEMICAL STRUCTURE AND BIOLOGICAL ACTIVITY 845 



related to vitamin K has been investigated by Fieser, Tishler, and Samp- 

 son. ^^ The data on the response are summarized in Tables 3 to 1 1 . Refer- 

 ences to the synthesis and characterization of the individual compounds are 

 included in each table. 



Table 3 shows the relative effectiveness of various substituents when 

 present in the place of R in 2-methyl-l,4-naphthoquinone. 



R-substituted-2-niethyl- 

 1 ,4-naphthoquinone 



Vitamin K2 has been shown to have between 62^^ and 67^^ per cent of the 

 activity of vitamin Ki, while its molecular weight is only 1.3 times as great. 

 On this basis, it has an activity of 82% of that of vitamin Ki. The maxi- 

 mum effect on the side chain is reached with a 20-carbon residue of isoprene 

 groupings; little further change occurs on further elaboration of the side 

 chain. The branched chain on carbon 3 seems to favor the antihemor- 

 rhagic effect, as the octadecyl compound is practically inactive.'^'' More- 

 over, when the farnesyl or geranyl group is introduced in the S-position, the 

 resulting derivatives are surprisingly potent. Although such compounds 

 have not been reported as occurring naturally, the corresponding alcohols — 

 farnesol and geraniol — are widely distributed in nature. 



(2) Effect of Substitution of 1 ,4--Naphthoquinone in Position 2 with Alkyl 

 and ^-Alkenyl Residues 



Fieser and his co-workers'^^ "^^ have been able to prepare a series of mono- 

 substituted naphthoquinones by direct condensation of the naphthohydro- 

 quinone with such alcohols as farnesol, phytol, and geraniol; these com- 

 pounds are similar to those studied earlier (see page 844), except that the 

 methyl group at position 2 is absent. Table 4 summarizes the results on 

 these monosubstituted naphthoquinones of the presence of various sub- 

 stituents in the place of R in 2-R-l,4-naphthoquinone. 



^8 L. F. Fieser, M. Tishler, and W. L. Sampson, /. Am. Chem. Soc, 62, 996 (1940). 



" L. F. Fieser, M. Tishler, and W. L. Sampson, /. Am. Chem. Soc, 62, 1628-1629 

 (1940). 



80 L. F. Fieser, M, Tishler, and N. L. Wendler, /. Am. Chem. Soc, 62, 2861-2866 

 (1940). 



