594 PANTOTHENIC ACID 



They recognized a rough similarity between their factor and pantothenic 

 acid but concluded that the available evidence was too limited to warrant 

 discussion of the relationship of the two factors. 



A clue to the nature of pantothenic acid was found with the discovery 

 that /3-alanine was a yeast growth stimulant. ^^ This discovery led Williams 

 and his coworkers to suspect that there was a structural relationship be- 

 tween j8-alanine and pantothenic acid. This suspicion was soon confirmed 

 with the discovery that j8-alanine was in fact a cleavage product of panto- 

 thenic acid/- and they succeeded in isolating it in the form of /3-naphthalene- 

 sulfo-|8-alanine. " They also found that their yeasts (G.M.) were capable of 

 synthesizing physiologically active pantothenic acid when /3-alanine was 

 supplied in the medium. ^^ 



Attention was now concentrated upon the other cleavage product. The 

 evidence indicated that it was an Q:-hydroxy-7-lactone.^* Elementary 

 analysis of the most potent pantothenic acid concentrates yielded the 

 misleading information that this lactone possessed five carbon atoms" 

 instead of the six actually present. A partial synthesis of physiologically 

 active pantothenic was effected by condensing /3-alanine ester with impure 

 lactone obtained from a pantothenic acid concentrate.^^ This amazing 

 information, obtained about a compound before it had been obtained in 

 pure form, proved to be decisive in the ultimate isolation and synthesis of 

 pantothenic acid. 



In the meantime, Snell ei al}^ continued their investigations of the acidic 

 compound required by lactic acid bacteria. In general their information 

 paralleled that obtained by Williams and his coworkers. They^^ also suc- 

 ceeded in accomplishing a partial synthesis of physiologically active panto- 

 thenic acid and concluded that their factor was indeed identical with the 

 pantothenic acid of Williams and his coworkers.^"' ^^' ^^ 



Norris and Ringrose^^ described in chicks a "pellagrous" dermatitis 

 which was destined to play a key role in the isolation and characterization 

 of pantothenic acid. The cure of the "pellagrous" condition was attributed 



" R. J. Williams and E. J. Rohrman, /. Am. Chem. Soc. 58, 695 (1936). 



12 H. H. Weinstock, Jr., H. K. Mitchell, E. F. Pratt, and R. J. Williams, J. Am. 

 Chem. Soc. 61, 1421 (1939). 



13 H. K. Mitchell, H. H. Weinstock, Jr., E. E. Snell, S. R. Stanberry, and R. J. 

 Williams, /. Am. Chem. Soc. 62, 1776 (1940). 



" R. J. Williams, H. H. Weinstock, Jr., E. Rohrmann, J. H. Truesdail, H. K. Mit- 

 chell, and C. E. Meyer, /. A??i. Chem. Soc. 61, 454 (1939). 



!"> R. J. Williams, H. K. Mitchell, H. H. Weinstock, Jr., and E. E. Snell, J. Am. 

 Chem. Soc. 62, 1784 (1940). 



i« E. E. Snell, F. M. Strong, and W. H. Peterson, /. Am. Chem. Soc. 60, 2825 (1938). 



" E. E. Snell, F. M. Strong, and W. H. Peterson, /. Bacteriol. 38, 293 (1939). 



18 L. C. Norris and R. C. Ringrose, Science 71, 643 (1930). 



