Chapter VD 



THE FOLIC ACID GROUP 



The isolation of members of the folic acid group brought together a 

 number of divergent studies. The earliest report of a biological activity 

 which can now be attributed to the folic acid group is the striking effect 

 of yeast extract in relieving a nutritional anemia occurring particularly 

 in pregnant women. 1 The nutritional deficiency was reproduced in 

 monkeys, 2, 3 and the factor necessary to prevent the deficiency was later 

 termed vitamin M. 4, 5 The folic acid group also accounts for the active 

 principles which were essential for growth (Factor U) 6 and prevention 

 of nutritional anemia (vitamin B c ) in chicks, 7, 8 and essential for the 

 growth of Lactobacillus casei (Norit Eluate Factor) 9,10 and of Strepto- 

 coccus faecalis R. 11 



The isolation of the first crystalline member of the folic acid group 

 was reported by Pfiffner et al., 12 who obtained folic acid from liver. 

 Shortly afterward, Stokstad 13 also reported the isolation of the same 

 compound from liver. An enzymatic digest of a yeast concentrate was 

 used as another source material for the isolation of the crystalline mate- 

 rial. 14 Folic acid has also been isolated in essentially pure form from 

 spinach. 15 Other members of this group of factors were obtained in crystal- 

 line form within a short period of time. 16, 17, 18 Structural studies on folic 

 acid indicated a xanthopterin-like unit, 1923 p-aminobenzoic acid, 21-23 

 and glutamic acid, 21-23 combined as indicated by the following formula: 



OH 



A N 

 N C C— CH 2 — NH— (/ J— CO— NH— CH— CH 2 — CH 2 — COOH 



H,N— C C CH ^=/ COOH 



\y \ / 



N N 



folic acid (N-pteroyl-h-glutamic acid) 



The complete structure and synthesis 24, 25 were announced simul- 

 taneously with the structure of another member of this complex, a factor 

 derived from the cultural broth of an unidentified organism belonging 

 to the genus Cory neb acterium. 11 This factor was identified as a pteroyldi- 



565 



