SYNTHESIS OF POLYPEPTIDES. 87 



Another method which has much greater application consists in the 

 anchoring of an amino-acid to a halogen of an acid radical, for example, by 

 the action of brompropionyl bromide or chloride upon glycocoll accord- 

 ing to the following equation: 



CH 3 CHBrCOCl + NH 2 CH 2 COOH = HC1 + CH 3 CHBrCO.NHCH 2 COOH 

 (brompropionyl glycine). On subsequent treatment with ammonia the 

 halogen (Br) is replaced by NH 2 and the dipeptide alanylglycine 



CH 3 CHNH 2 CO.NHCH 2 COOH 



is obtained. By the second action of brompropionylchloride and then 

 treatment with NH 3 we introduce a new alanyl group and the tripeptide 

 alanyl-alanyl glycine is prepared. By the action of a halogen derivative 

 of an acid radical another amino-acid residue can be introduced, and the 

 chain of amino groups can be thus extended. 



The prolongation of the chain on the other side, namely, at the car- 

 boxyl, FISCHER has accomplished by chlorination of the amino-acids 

 by special treatment with phosphorus pentachloride. The carboxyl is 

 thus transformed into COC1, while the acid at the same time fixes a 

 molecule of HC1, for example CH 3 CHNH 2 HCL 



COC1 



Just as in the case of the carboxyl group of an amino-acid, so also can 

 a polypeptide or its halogen acyl combination be chlorinated and then 

 combined with a new amino-acid, or a new peptide. As an example, 

 FISCHER, from a-bromisocapronyldiglycyl glycine, first prepared a-brom- 

 isocapronyldiglycylglycyl chloride, and then with diglycylglycine he 

 obtained the heptapeptide leucyl-pentaglycylglycine, 



C 4 H 9 CH(NH 2 )CO.(NHCH 2 CO) 5 .NHCH 2 COOH. 



For the various combinations of the optically active amino-acids to 

 polypepteids it was important to possess methods of preparation of these 

 amino-acids, and for this purpose FISCHER in many cases used the 

 so-called WALDEN'S reversion. This consists in that one optically active 

 amino-acid, for example the Z-form, is transformed into the corresponding 

 halogen fatty acid by the action of nitrosyl bromide, yielding the opti- 

 cal antipode the d-form. By the action of ammonia the d-amino-acid 

 is now obtained which in the above-mentioned manner can be retrans- 

 formed into the Z-form. Thus from d-leucine we first obtain Z-bromisoca- 

 proic acid and then by the action of ammonia Z-leucine and in the prepara- 

 tion of the polype*ptides the same occurs. Thus, for example, if by 

 reversion d-leucine is changed first into Z-bromisocapronyl chloride, if 

 this last is combined 'with Z-leucine, then*we obtain the dipeptide Z-leucyl- 



