THE SYNTHESIS OF THE PROTEINS 27 



of a- S-dibromo valeric acid chloride reminds us of the synthesis of pro- 

 line, where when the compound is treated with ammonia in order to 

 exchange the Br atoms for NH 2 , ammonia is lost and ring formation 

 occurs. Prolyl-alanine is prepared as follows : 



CH 2 Br . CHo . CH 2 . CHBr . COC1 + NH 2 . CH(CH 3 ) . COOH 



= HC1 + CH 2 Br . CH 2 . CH 2 . CHBr . CO NH . CH(CH 3 )COOH 



CH 2 Br . CH 2 . CH 2 . CHBr . CO NH . CH(CH 3 ) . COOH + 3 NH 3 



= 2 NH 4 Br + CH 2 . CH 2 . CH 2 . CH . CO NH . CH(CH a )COOH 



NIT 



In order to introduce the asparagyl group into an amino acid, chloro- 

 succinyl chloride, the corresponding halogen-acyl chloride, cannot be 

 employed, since on treatment with ammonia it yields fumaryl derivatives. 

 These, however, when heated with strong ammonia again take up am- 

 monia forming the asparagyl compound, and hence can be employed for 

 this purpose. 



These radicals can be introduced into all the simple mono-amino 

 acids, such as alanine, leucine, tyrosine, etc. ; also into cystine and the 

 dicarboxylic acids when the compounds such as dialanyl-cystine and 

 asparagyl-dialanine are formed. They can also be introduced into the 

 molecule of a di, tripeptide, etc., as can be seen from the appended list 

 of polypeptides synthesised by this method, which, however, only allows 

 of the chain of amino acids being lengthened on one side, namely, at 

 the amino group end. 



The majority of the polypeptides synthesised by this method are 

 optically inactive, but the optically active compounds can also be pre- 

 pared by employing the optically active halogen-acyl chloride. As 

 previously described under the optically active amino acids, these com- 

 pounds undergo the Walden inversion ; the method therefore allows of 

 the whole of an inactive amino acid being employed for the synthesis 

 of an optically active polypeptide ; thus dl-leucine after separation into 

 d-leucine and 1-leucine can be converted into 1-leucyl-l-leucine by pre- 

 paring the d-bromisocapronyl chloride from the d-leucine and combining 

 it with 1-leucine ; treatment with ammonia gives 1-leucyl-l-leucine as 

 the compound undergoes the Walden inversion. The four isomers 



d-leucyl -1-leucine \ d-leucyl-d-leucine ^ 



1-leucyl-d-leucine j 1-leucyl-l-leucine J 



can be thus prepared. The A compound is the former inactive leucyl- 

 leucine. Also 1-phenylalanyl-glycine was obtained from d-phenyl-a- 

 bromopropionylchloride and glycine, and glycyl-1-phenylalanine from 

 chloracetylchloride and 1-phenylalanine, the dl-phenylalanine used 

 having been separated into its optical isomers by means of its formyl 

 compound. 



