THE POLYPEPTIDES. 



Synthesis. 



The three methods which have been devised by Fischer for the 

 synthesis of the polypeptides have been mentioned in the introduction. 

 A description of all the polypeptides which have been prepared is 

 impossible, but Tables have been compiled giving the compounds 

 obtained by the various methods. A fuller account of the methods 

 is also necessary for the proper comprehension of the enormous work 

 which has been expended on the synthesis of the higher polypeptides. 



Method I. By Formation and Hydrolysis of the Anhydrides 



( Diketopiperazines). 



It had been found by previous investigators that leucine, alanine 

 and other amino acids were converted on heating into anhydrides. 

 Curtius and Goebel, in 1 888, showed that glycine ester was decomposed 

 by water, or by distillation, and was converted with loss of alcohol into 

 an anhydride which probably had the formula : 



NH CH, CO 



CO CH a NH 



These anhydrides form the starting-point in the synthesis of the 

 polypeptides by this method, and they are best obtained by heating the 

 ester of the amino acids in a sealed tube to 1 50-180 C. for some hours. 



Fischer and Fourneau, in 1901, found that glycine anhydride was 

 converted by boiling with concentrated hydrochloric acid into the 

 hydrochloride of an amino acid of the formula C 4 H 8 N S O, ; from this 

 they obtained the free acid by treatment with the calculated quantity 

 of caustic soda, or by means of silver oxide, and represented its for- 

 mation by the equation : 

 NH CH, CO 



CO CH, 



The new compound is the first anhydride of glycine, and it was 

 termed glycyl-glycine, the group NH, . CH,.CO being called the 

 glycyl group. 



Glycyl-glycine ester resulted when glycine anhydride was treated 

 with alcoholic hydrochloric acid : 

 NH CH, CO 



CH,- 



J I + H,O = NH,.CH,.CO NH.CHj.COOH. 



+ C,H 8 OH = NH, . CH, . CO NH . CH, . COOC.H, . 

 CO CH, NH 



