PANTOTHENIC ACID 



and T. H. Jukes.® The complete synthesis, described by Stiller et 

 al.,'' was as follows : 



K.C03 ^^' ^^^ + 



H.CHO + (CH3)2CH . CHO — i-i> CH^OH . C . CHO ^aHSor 



CH3 

 CH3 CH3 



HCl ' /3-alanine 



CHoOH . C . CHOH . CN ^ CHo . C . CHOH . CO > Pantothenic acid. 



CH3 



CH, 



Synthetic pantothenic acid proved to have only half the growth- 

 promoting action of the natural acid on Lactobacillus helveticus, but 

 Stiller et aW resolved the sodium salt of pantoic acid into its optically 

 active isomers by treatment with quinine hydrochloride, and then 

 reacted each separately with j3-alanine ester, obtaining in this way 

 D- and L-pantothenic acid. The former was active on micro-organisms, 

 rats and chicks, whilst the latter was inactive. 



A different synthesis was later described by D. W. Woolley.^ The 

 sodium salt of pantoic acid was converted via the acetyl derivative 

 into the acid chloride, which was coupled with j8- alanine in aqueous 

 solution in the presence of alkali. 



The synthesis of racemic pantothenic acid was also described by 

 T. Reichstein and A. Griissner,^ who used a similar method to that of 

 Williams et al. They resolved pantolactone with quinine and, in a 

 later paper,^^ described the resolution of pantothenic acid with quinine 

 or cinchonidine methydroxide and noted the biological activity of the 

 optically active pantothenic apids, confirming the results obtained by 

 Williams and his co-workers. M. Gatzi-Fichter et al}'^ prepared the 

 crystalline sodium salt of pantothenic acid by hydrolysis of the ester 

 with baryta and decomposition of the barium salt. 



R. T. Major and J. Finkelstein ^^ resolved pantolactone by means 

 of the methydroxides of quinine, quinidine and cinchonine, whilst 

 E. T. Stiller and P. F. Wiley ^^ used quinine methydroxide for resolving 

 racemic pantothenic acid itself. They stated that the alkaloids were 

 not sufficiently strong bases to give stable salts of pantothenic acid, 

 whereas the methydroxides, being more strongly basic, gave salts 

 sufficiently stable to enable the pure D- and L-salts to be separated ; 

 these yielded D- and L-pantothenic acid respectively on decomposi- 

 tion. Pantolactone has also been resolved with the aid of brucine 

 and of diacetyl-D-tartaric anhydride.^* 



R. Kuhn and T. Wieland ^^ described the preparation of a concen- 

 trate from fish liver of a factor which stimulated the growth of Strepto- 

 bacterium plantarum. This concentrate yielded on hydrolysis ^-alanine, 



354 



