PANTOTHENIC ACID 



one other factor. Factor W, like pantothenic acid, was not adsorbed on 

 fuller's earth, but differed in not being extracted from aqueous solutions 

 by ether, and in its stability to alkali. D. V. Frost and C. A. Elvehjem 

 noted a close resemblance between factor W and Macrae's filtrate factor. 

 D. W. Woolley ^^ found that an alcohol-soluble fraction from an aque- 

 ous liver extract gave increased growth in rats over and above that 

 obtained with pantothenic acid ; biotin was inactive. 



H. Kringstad and G. Lunde ^® obtained a growth factor, to which 

 they gave the name factor Bw, which resembled factor W in many 

 respects. It differed from the eluate factor, however, in not being 

 precipitated by phosphotungstic acid and from the filtrate factor in 

 not being extracted by ether at pH i. 



The first real clue to the structure of the non-alanine portion of 

 pantothenic acid was provided by Y. SubbaRow and L. Rane,^® who 

 coupled the acid chloride of acetylated aS-dihydroxyvaleric acid 

 (prepared by deamination of ornithine) with j3-alanine ethyl ester and 

 found that, whilst the product stimulated the growth of a strain of 

 haemolytic streptococcus, it was required in larger amounts than was 

 calcium pantothenate or the calcium salt isolated from liver. It was 

 inferred from this that pantothenic acid was related to, but not 

 identical with, a8-dihydroxyvaleryl-/S-alanine. 



G. H. Hitchings and D. W. Woolley ^^ found that pantothenic acid 

 could be replaced by a dihydroxycaproyl-j3-alanine in the growth of a 

 strain of haemolytic streptococcus. The nature of the substituted 

 caproic acid used was not disclosed, but in the following year R. J. 

 Williams and R. T. Major ^i announced the preparation from crude 

 barium pantothenate of a pure lactone, mp. 91 to 92° C, identified as 

 a-hydroxy-jSj3-dimethyl-y-butyrolactone. This, when coupled with 

 j3- alanine, yielded racemic pantothenic acid : 



CH,.C.CHOH.CO + NH^.CHa.CH^.COOH 



I CH, I 



! O 



CH, 



> CH2OH . C . CHOH . CO . NH . CH2 . CHa . COOH 



CHs 



a-Hydroxy-jS/3-dimethyl-y-butyrolactone is now commonly referred to 

 as pantolactone and the corresponding acid as pantoic acid. 



References to Section 1 



I. C. A. Elvehjem and C. J. Koehn, Nature, 1934, 134, 1007 ; /. Biol. 

 Chem., 1935, 108, 709. 



350 



