140 THE PROTEINS AND THE AMINO-ACIDS 



On now treating the glycyl-glycine chloride with silver oxide, silver 

 chloride is precipitated and free Glycyl-glycine is obtained. If, how- 

 ever, the glycine anhydride be originally treated with Alcoholic instead 

 of with an aqueous solution of hydrochloric acid, the ethyl ester of 

 glycyl-glycine is obtained: 



xCH 2 .NHv /CH 2 NH 2 



C C = O + C*H 6 OH = O=C 



\ / \ 



(Glycine anhydride.) (Glycyl-glycine ester.) 



It would appear, therefore, as if we had only to repeat this cycle 

 of operations indefinitely in order to secure the most complex poly- 

 amino-acids; but this is not so easy as it might appear at first sight; 

 the instability of polyamino-acids consequent upon the high reactivity 

 of the NH 2 group, and the consequent difficulty of obtaining simple 

 anhydrides renders this procedure impossible. Moreover the anhy- 

 dride-ring is in many cases (e. g., leucine anhydride) very difficult to 

 break up when it has once been formed. 



In the search for methods of overcoming these difficulties Fischer 

 found that the instability of the amino-acids could be eliminated by the 

 introduction of radicals into the NH 2 group, and he and Fourneau 

 synthesized phenylcyanate-glycyl-glycine (C 6 H5.NH.CO-NHCH 2 CO 

 -NHCH 2 COOH) and carboxethyl-glycyl-glycine ester (C 2 H 5 O.OC. 

 NH.CH^CO-NH.CH^COOC,!^ which are both chemically stable 

 bodies. In subsequent investigations Fischer found that, by gentle 

 heating, combination between the esters of the carboxethyl-amino- 

 acids and other amino-acids could be directly brought about, and in 

 this way carboxethyl-diglycyl-leucine ester was formed: 



C 2 H 6 OOC.NH.CH 2 CO.NH.CH 2 .CO.NH.CH.(C4H 9 )CO.OC2H 5 . 



The difficulty was here encountered, however, that the carboxethyl- 

 group having been once introduced, cannot be eliminated again. 



The method which was devised to overcome this difficulty was 

 extremely ingenious. The introduction of a radical into the NH 2 

 group appeared to be a necessity, forced upon us by the impossibility 

 of otherwise securing simple anhydrides of the acids. It occurred to 

 Fischer, however, that the radical thus introduced into the NH 2 

 group might itself be made a carrier of amino-acid groups into the 

 molecule. This anticipation proved to be correct. The radical which 

 was first utilized was the chloracetyl group (C1CH 2 .CO ). When 

 chloracetyl chloride is allowed to act upon glycyl-glycine ester (ob- 

 tained by the methods described above), chloracetyl-glycyl-glycine- 

 ester is obtained: 



C1CH 2 COC1 + H 2 N.CH 2 CO.NH.CH 2 COOC 2 H 6 = 

 Chloracetyl chloride) + (Glycyl-glycine ester) = 



C1CH 2 .CO.NH.CH 2 .CO.NH.CH 2 .COOC 2 H 5 + HC1 



(Chloracetyl glycyl-glycine ester) . 



