ANALOGUES 



pantothenic acid " (a-hydroxy - jSjS - bishydroxymethyl - butyryl - j8 - 

 alanine), with appreciable pantothenic acid activity ; this had 20 % 

 of the activity of pantothenic acid when tested on Lactobacillus hel- 

 veticus. E. Zschiesche and H. K. Mitchell ^^ also observed some 

 activity in a-hydroxy-j8j8-bishydroxymethyl-butyryl-jS-alanine when 

 tested on rats. 



T. Reichstein and A. Griissner ^' reported that ay-dihydroxyvaleryl- 

 jS-alanine and a8-dihydrox3rv^aleryl-^-alanine had the same activity 

 as /3-alanine on rats, but were inactive on lactic acid bacteria. Mention 

 has already been made (page 354) of the inactivity of the compound 

 prepared by R. Kuhn and T. Wieland by coupling ^-alanine with the 

 lactone, C17H12O3. 



Several derivatives of ^-alanine were prepared by J. W. Barnett 

 and F. A. Robinson ^^ and were shown by H. Mcllwain ^^ to have 

 practically no stimulating action on the growth of Streptococcus hae- 

 molyticus, Staphylococcus aureus or Proteus morganii. The following 

 had only 5 x io~® of the activity of pantothenic acid : y-hydroxy-n- 

 butyryl-^-alanine, jSS-dihydroxy-yy-dimethylvaleryl-^-alanine (" homo- 

 pantothenic acid "), y-hydroxy-jS^-dimethylbutyryl-^-alanine (" de- 

 soxypantothenic acid "), 8-hydroxy-yy-dimethyl-/l*-^ -pentenoyl-/S-ala- 

 nine (" dehydrohomopantothenic acid ") and pantoyltaiuamide, 

 whilst pantoyltaurine, homopantoyltaurine and y-hydroxy-fj-butyryl- 

 /S-alanine had no growth-promoting action. jS-Ethyl-ay-dihydroxy- 

 ^-methyl-butyiyl-^-alanine had less effect than pantothenic acid on 

 S. plantarum}'^"' These results emphasise the high degree of structural 

 specificity of pantothenic acid. 



Several of these compounds were found to inhibit the growth of 

 bacteria for which pantothenic acid is an essential growth factor 

 (see page 397). 



The j8-alanides of a- and y-hydroxy-j8j3-dimethylbutyric acid and 

 j8y-dihydroxy-jS-methylbutyric acid had a slight growth-stimulating 

 activity on Acetobacter suboxydans, L. arabinosus and Gebrtider- 

 Mayer yeast, possibly owing to hydrolysis with liberation of /S-alanine.^^ 



The ethyl ester of DL-a-amino-y-hydroxy-/3j8-dimethyl-butyryl-^- 

 alanine had no pantothenic acid activity when tested on rats or 

 L. arabinosttsP°' It has been suggested that the corresponding amino 

 acid, a-amino-y-hydroxy-jS^-dimethyl-butyric acid (pantonine), is the 

 precursor of pantoic acid in the synthesis of pantothenic acid.^^b fhe 

 keto-acid corresponding to pantothenic acid, namely y-hydroxy-a-keto- 

 j8j8-dimethyl-butyryl-/3-alanine, likewise had no biological activity.^^^ 



Analogues Derived from Amino Acids other than ^-Alanine 



Replacement of the /S-alanine portion of pantothenic acid by other 

 amino acids invariably leads to loss of activity. Thus, Weinstock et 



395 



