VITAMIN RESEARCH 



of the structure of pantothenic acid under tliese conditions was accom- 

 phshed by a rather unique series of developments. ^-Alanine was 

 first reported by WiUiams, Weinstock, and Mitchell (61,68) to be 

 formed from this calcium salt in acid or alkaline medium. The other 

 hydrolytic product was found (34) to l)e an a-hydroxy acid capable 

 of spontaneous transformation to a lactone. The crude lactone 

 fraction was recombined (66,72) with /3-alanine to give material which 

 possessed the physiological activity of pantothenic acid and, of course, 

 actually was this acid. This condensation reaction constituted re- 

 synthesis, and the results supported the earlier observation (34) that 

 /3-alanine was combined as an amide through its /3-amino group, as 

 in structure I. At this stage of the investigation it was clear that it 



R— CONHCH2CH.2CO..H 



(I) 



would be unnecessary to isolate pure pantothenic acid if the hydroxy 

 acid fragment or its lactone could be isolated in pure form. The 

 structure determination of the hydroxy acid would give also the struc- 

 ture of pantothenic acid. Further research (34,53) showed how con- 

 centrates containing only 3 to 40% of pantothenic acid could be 

 purified and treated so as to yield the pure lactone. Once having 

 obtained the pure lactone, Stiller, Keresztesy, and Finkelstein (53) 

 applied degradation reactions which showed the lactone to be a- 

 hydroxy-/3,/3-dimethyl-7-butyrolactone (II) : 



OH 



CH— C=0 OH 



(CH3)2G O (CH,)2C-CH-CONHCH2CH2C02H 



\ / 1 



CH^ CH,OH 



(II) (III) 



Obviously, pantothenic acid was rt,7-dihydroxy-/3,/3-dimethylbutyryl- 



/3'-alanide (III). 



Because of the great cost and technical difficulties in the isolation 

 of new vitamins, it has been necessary on occasion to open the program 

 of structural research with a series of studies which are designed to 

 cliaractcrize the functional groups of the substance and which can be 



93 



