642 THE BIOCHEMISTRY OF B VITAMINS 



that the last compound is not so effective as either the w-butylamine 

 or ethanolamine derivative. 82 DL-N-Pantoyl-/3-diethylaminoethylamine, 

 DL-N-pantoyl-5-diethylamino-2-pentylamine, and DL-N-pantoyl-p-anisi- 

 dine are essentially inactive as pantothenic acid antagonists for Lacto- 

 bacillus casei. 62 



N-Substituted /3-Alanines and Related Compounds. Modification of the 

 pantoyl group of pantothenic acid has resulted with few exceptions in 

 compounds possessing slight activity in replacing the vitamin or in com- 

 pounds with neither stimulatory nor inhibitory properties. Almost one- 

 third of the reported N-substituted /^-alanine analogues of pantothenic 

 acid are active at least partially in replacing the vitamin in the nutrition 

 of some organisms (cf. Table 24). 



The N-substituted derivatives of /3-alanine which have been found to 

 be inactive in replacing pantothenic acid are listed in Table 32. The 

 ester of a-amino-y-hydroxy-/?,/?-dimethylbutyryl-/?-alanine, although in- 

 active alone in replacing pantothenic acid, supplements suboptimal con- 

 centrations of pantothenic acid in stimulating growth of Lactobacillus 

 arabinosus. As indicated in Table 32, nearly half of these compounds 

 were not tested as possible antimetabolites of pantothenic acid. Although 

 many of the compounds were found to be slightly inhibitory to the test or- 

 ganisms, the inhibitions were with few exceptions not prevented by panto- 

 thenic acid. Thus, y-hydroxyvaleryl- and y-hydroxybutyryl-/3-alanine 

 prevent the growth of several organisms, but the toxicity is not abolished 

 by pantothenic acid. 



Salicylyl-/3-alanine, mandelyl-/?-alanine, and acetyl mandelyl-/3-alanine 

 have been reported to be moderately active pantothenic acid antagonists ; 

 however, the data presented for mandelyl-/?-alanine do not indicate a 

 competitive inhibition. 



Drell and Dunn 73, 84 have shown that N-a,y-dihydroxy-/?,/?-dimethyl- 

 valeryl-/3-alanine (w-methylpantothenic acid) competitively prevents the 

 utilization of pantothenic acid by a large number of lactic acid bacteria 

 and by Streptococcus hemolyticus. This compound is the first N-substi- 

 tuted /^-alanine to be reported as an effective antimetabolite of panto- 

 thenic acid. The analogue exists in two racemic diastereoisomeric forms, 

 the relative activities of which are unknown. 



As indicated in Table 33, w-methylpantothenic acid inhibits the growth 

 of a wide variety of organisms for which pantothenic acid is essential; 

 however, it does not affect the growth of organisms not requiring the 

 vitamin for growth. As is common with a number of inhibitors, stimulation 

 of growth was obtained in many instances at concentrations of the an- 

 alogue just lower than that necessary for inhibition of growth. At rela- 

 tively high concentrations of pantothenic acid, the inhibition index was 



