280 



VI. ACETIC, FORMIC, AND PROPIONIC ACIDS 



(S) The Nature of the Active Formyl Group 

 It now appears that the "formyl" group behaves in a manner similar to 

 that of the "acetyl" group. Thus, for the participation of formate in 

 various syntheses, it is necessary that it occur as "active formate." It is 

 believed that this "active" compomid is the citrovorum factor (CF), or 

 Leuconostoc citrovorum factor (LCF). This is also referred to as folinic 

 acid-SF, and as leucovorin. Although there is no absolute proof that CF 

 actually transports the formate radicle, there is considerable circumstantial 

 evidence to support this hypothesis. Thus, a A^-formyl group actually 

 occurs in the CF molecule; the chemical designation for this factor is 

 5-formyl-5,6,7,8-tetrahydropteroylglutamic acid, or 5-formyl-5,6,7,8-tetra- 

 hydrofolic acid. Moreover, it is known that this formyl group may be 

 lost without markedly altering the CF activity. ^^^ If the CF molecule 

 functions in reactions through which the formyl radicle is alternately 

 gained and lost while it still maintains its other functions, the possibility 

 that it acts as a transformylating agent is greatly increased. An equation 

 illustrating how CF may participate in this reaction is given below: 



H H 



H 



H 



N 



OH C. 



H 



N 



H C— N— c/ 



/- 



^O H 



.H 



H 



-C, 



H 



O H H 

 C— C— N— C— COOH 



CHo— CH2— COOH 



Citrovorum factor 



+ H0H 



-HOH 



HoN— C 



N 



C— H 



l/H 

 C< H H 



C 



OH 



^C— N— C^ 

 H 



H 



'^C= 

 H 



H 



=c/ 



H 



O H H 

 'C— C— N— C— COOH + HCOOH 



CH2 



5,6,7,8-Tetrahydropteroylglutamic acid 



-CH2— COOH 



Formic 



acid 



The Transformation of CF to 5,6,7,8-Tetrahydropteroylglutamic Acid with the 



Formation of Formate. The reverse reaction also occurs. The figures in the 



circles represent the position numbers adopted for this compound. 



1" H. P. Broquist, M. J. Fahrenbach, J. A. Brockman, Jr., E. L. R. Stokstad, and 

 T. H. Jukes, J. Am. Chem. Soc, 73, 3535-3536 (1951). 



