AUGUST 19, 1&21 ALSBERG : PHYSIOLOGICAIv CHEMISTRY 339 



vanillyl-decenoyl amide. ^^ 



OCH3 



HO—/ y—CUt NH COC9H17 



He thereupon made a series of homologous vanillyl-acyl amides with 



acids of different molecular weights.^' He found that with increasing 



molecular weight there was an increase in pungency up to a maximum 



beyond which it decreased. Table 2 gives the relative pungency of 



these substances, capsaicin being rated at one hundred. 



TABLE 2. — Comparative Pungencibs of Vanillyl-Acyl Amides 



Vanillyl n-hexoylamide 5 



Vanillyl n-heptoylamide 25 



Vanillyl n-octoylamide 75 



Vanillyl n-nonoylamide 100 



Vanillyl n-decoylamide 50 



Vanillyl n-undecoylamide 25 



Vanillyl n-dodecoylamide 25 



Vanillyl undecenoylamide 25 



This phenomenon of increasing intensity of physiological action 

 up to a maximum with increase in molecular weight and a diminution 

 beyond the maximum with still further increase in molecular weight is 

 a phenomenon that has been observed frequently. ^^ There is good 

 reason to believe that it is due, in part at any rate, to changes in 

 solubility. For example, for a substance to be odorous it must be 

 sufficiently soluble in both water and lipoids, since the cells of the 

 mucous membrane of the nose are covered by a watery fluid and have 

 in all probability a lipoid semi-permeable cell membrane. ^^ Thus 

 in the homologous series of pungent substances of table 2 the solubility 

 in water decreases with rising molecular weight while the solubility 

 in ether increases. Perhaps this is a plain case in which the manner 

 of action, that is, pungency, is a function of the chemical structure 

 of the molecule, while the intensity of action is dependent upon the 

 physical property of solubility. Perhaps the specificity of the pungent 

 action is not to be sought in the substances so much as in the taste 

 buds of the tongue, according to the well-known physiological law of the 

 specific response of the nerve end-organs. Any stimulus gives the 



*^ E. K. Nelson. The constitution of capsaicin, the pungent principle of capsicum. 

 Journ. Amer. Chem. Soc. 41: 1115. 1919. 



*'' E. K. Nelson. Vanillyl-acyl amides. Journ. Amer. Chem. Soc. 41: 2122. 1919. 

 *^ Th. H. Durrans. The relationship between odour and chemical constitution. Per- 

 fumery and Essential Oil Record 10: 107-132. London, May 21, 1919. 

 *' Backmann. Journ. physiol. path. gen. 17: 1. 



