108 SCIENCE PROGRESS 



temperature produced the same result in fifteen to twenty- 

 minutes. The diketopiperazines of alanine, leucine, phenyl- 

 alanine, tyrosine are thus easily prepared, as also the corre- 

 sponding dipeptide. As yet the dipeptides of the diamino 

 acids, lysyllysine and histidylhistidine and serylserine, have 

 only been obtained by this method by Fischer and Suzuki ; 

 in these cases the methyl ester of the amino acid was more 

 easily converted into the diketopiperazine. The method does not 

 lend itself to the preparation of mixed diketopiperazines. These 

 are obtained by the action of ammonia on the a-halogenacyl 

 derivative of the amino acid ester, e.g. glycylalanine anhydride, 



Cl . CH 2 . CO . NH . CH(CH :i ) . COOC,H 5 + 2NH3 = NH 4 C1 + C,H 5 OH + 



/CH...CO 

 NH< >NH 



\CO . CH.CH 3 



The simple method of combining the acid chloride of an 

 amino acid with another amino acid for the synthesis of 

 polypeptides could not be employed, as these derivatives 

 were unknown and impossible to prepare. The carbethoxy 

 derivative, however, of the amino acid, or polypeptide, when 

 warmed with thionylchloride, was found to give the acid 

 chloride, and this compound reacted with the esters of amino 

 acids or polypeptides to form the carbethoxy derivates of 

 polypeptides, thus carbethoxyglycylglycine on treatment with 

 thionylchloride yielded the acid chloride which reacted with 

 glycylglycinester to form the carbethoxy derivative of tri- 

 glycylglycinester. The conversion of this compound into the 

 true tetrapeptide, owing to the firm union of the COOH group, 

 was not possible, and a third method, which reminds us of 

 the preparation of the amino acids, was attempted, and proved 

 most fruitful. 



This method consists in introducing an a-halogenacyl residue 

 into the molecule of an amino acid or polypeptide, and then 

 treating this compound with ammonia, whereby the Cl is 

 exchanged for NH 2 ; thus chloracetyl tyrosine, obtained from 

 chloracetyl chloride and tyrosine, on treatment with ammonia 

 gives glycyltyrosine, 



CH.,C1.C0C1 + HOOC.CH(NH !i ).CH.,.C 6 H 4 OH = HC1 + 

 HOOC . CH(NH . CO . CH..C1) . CH 2 . C 6 H 4 OH 

 . HOOC . CH(NH . CO . CH,C1) . CH 2 . QH.OH + NH, = HC1 + 

 HOOC . CH(NH . CO . CH,. NH,) . CH,.QH 4 OH 



