108 PTEROYLGLUTAMIC ACID 



Dihydro R — CHO + PGA in formic acid, followed by hydrolysis^^ 



R— CHO + PABG with catalytic hydrogenation^^- ^^ 



R — CH2OH + p-nitrobenzoylglutamic acid with catalytic hydrogen- 



ation^" 

 R — CH2OH + p-aminobenzoylgliitamic acid^^ 

 R — CH3 bromiuated + p-amiuobeiizoylgkitamic acid^^ 



R — CHo — N<^ // + p-amiiiohenzoylglutamic acid'^' ^^ 



I- 



R — CH — COOH + p-aminobenzojdglutamic acid'^^ 



I 

 Br 



3. Synthesis of Pteroylpolyglutamic Acid Derivatives 



The isolation of pteroyltrigliitamic acid from a fermentation product and 

 the existence of pteroylheptaglutamic acid in yeast made the synthesis of 

 various polyglutamic acid derivatives of pteroic acid a problem of interest. 

 The findings of Lewisohn el al}^ that pteroyltriglutamic acid from a fer- 

 mentation product caused spontaneous regression of mammary tumors in 

 mice also attached a special interest to the synthesis of this type of com- 

 pound. Pteroyl-a-glutamylglutamic acid was prepared by Mowat ei al}'" 

 and found to be 0.5 % as active as pteroylglutamic acid by *S. faecalis assay 

 and 0.8% by L. casei, and fully active for chicks. Pteroyl-a:,7-glutamyldi- 

 glutamic acid was 0.14% active by S. faecalis and 0.17% by L. casei. 

 Pteroyl-7-glutamylglutamic acid (Boothe et al.^^) is 71 % active by S. 

 faecalis and 63 % by L. casei assay. In both cases pteroylglutamic acid was 

 used as a standard. Pteroyl-7-glutamyl-7-glutamylglutamic acid had an 

 activity of 2.5% by S. faecalis and 71 % by L. casei. These activities are 

 very similar to those observed for pteroyltriglutamic acid isolated from a 

 fermentation product (Hutchings et al.^^). 



^8 F. Weygand, V. Schmied-Kowarzik, A. Wacker, and W. Rupp, Chem. Bcr. 83, 460 



(1950). 

 59 Roche Products, Ltd., Brit. Pat. 628,305 (March 15, 1948). 



«o H. Spiegelherg (to Hoffmann-LaRoche, Inc.), U. S. Pat. 2,487,393 (Nov. 8, 1949). 

 " J. Semb (to American Cyanamid Co.), U. S. Pat. 2,491,285 (Dec. 13, 1949). 



62 M. E. Hultquist (to American Cyanamid Co.), U. S. Pat. 2,473,796 (June 21, 1949). 



63 R. Tschesche, F. Korte, and R. Petersen, C/iew. Ber. 84, 579 (1951). 



6'' R. Lewisohn, C. Leuchtenbei;ger, R. Leuchtenberger, and J. C. Keresztesy, Science 



104, 436 (1946). 

 6U. H. Mowat, B. L. Hutchings, R. B. Angier, E. L. R. Stokstad, J. H. Boothe, 



C. W. Waller, J. Semb, and Y. SubbaRow, ./. Am. Chcm. Sac. 70, 1096 (1948). 

 «" J. H. Boothe, J. H. Mowat, B. L. Hutchings, R. B. Angier, C. W. Waller, E. L. R. 



Stokstad, J. Semb, A. L. Gazzola, and Y. SubbaRow, ./. jUn. Chem. Sac. 70, 1099 



(1948). 



