THE FOLIC ACID COMPLEX 



Fermentation L. casei Factor 



Pteroyl-y-glutamyl-y-glutamyl-glutamic acid was synthesised ^^ by 

 reacting diethyl glutamate with the acid chloride of a-ethyl carbo- 

 benzoxyglatamate to give the carbobenzoxy dipeptide, hydro- 

 genating to remove the protective benzyl group giving triethyl y-glut- 

 amylglutamate, and then repeating the series of reactions with another 

 molecule of a-ethyl carbobenzoxy glutamate acid chloride, and finally 

 hydrolysing the tetraethyl ester of y-glutamyl-y-glutamylglutamic acid 

 and converting to the pteroyl derivative. 



A simplified method was subsequently described.^^ The ^-nitro- 

 benzoyl derivative of y-ethyl glutamate was converted via the 

 y-hydrazide into the y-azide, which was reacted either with triethyl 

 y-glutamylglutamate, giving triethyl _/)-nitrobenzoyl -y-glutamyl- 

 y-glutamylglutamic acid direct, or with y-ethyl glutamate, giving 

 y-ethyl ^-nitrobenzoyl- y-glutamylglutamate which was converted 

 into the tripeptide by a repetition of the same procedure. The p- 

 nitrobenzoyl derivative was then reduced and the amino compound 

 converted into pteroyltriglutamate. 



SLR Factor (Rhizopterine) 



Rhizopterine was synthesised by treating synthetic pteroic acid 

 with formic acid.^* 



Xanthopterine 



Xanthopterine was synthesised by R. Purrmann ^^ by reacting 



2:4: 5-triamino-6-hydroxy-pyTimidine with dichloroacetic acid and 



then cyclising the resulting 2 : 4-diamino-5-dichloroacetylamino-6- 



hydroxy-pyrimidine by treatment with silver oxide : 



N=C . OH N==C . OH 



II II 



H2N . C C . NH . CO . CHCI2 > H2N . C C— N=C . OH 



II II II II I 



N— C . NH2 N— C— NrrrCH 



The starting material was prepared by the condensation of guanidine 

 with phenylazocyanoacetic ester and reduction of the azo group in the 

 product : 



NH2 COOC2H5 N=C . OH N=C . OH 



II II II 



I.C-I-CH N^.CeHs > H2N C C.Ng.CeHs > H2N . C C . NH2 



II I II II II II 



NH CN N— C . NH2 N— C . NH, 



Xanthopterine can also be prepared in good yield by reduction of 



leucopterine ; ^^ dihydroxanthopterine is formed on further reduction. 



476 



