THE SYNTHESIS OF THE PROTEINS 39 



had been obtained by heating inactive alanine ester; this probably 

 represents the inactive mixture of the dextro and laevo anhydrides; 

 the other compound 1-alanine anhydride has not yet been prepared. 

 The several forms of the diketopiperazines were synthesised in 1907 

 by Fischer and Koelker, who prepared 



1. d-leucine anhydride from d-leucyl-d-leucine ester and ammonia ; 



2. 1-leucine anhydride from 1-leucyl-l-leucine ester and ammonia; 



3. trans-leucine anhydride from d-leucyl-1-leucine ester and am- 

 monia and from 1-leucyl-d-leucine ester and ammonia. 



Hydrolysis by alkali of these anhydrides should give the correspond- 

 ing dipeptide, but in the case of the aminobutyryl-aminobutyric acid 

 anhydrides Fischer and Raske have found that a steric rearrangement 

 occurred ; the dipeptide A was obtained both from the anhydride A and 

 B ; these had been prepared by the action of ammonia on the respective 

 inactive esters, so that in this manner the dipeptide B can be converted 

 into the dipeptide A. 



The number of isomers of diketopiperazines containing two mole- 

 cules of different amino acids is greater than when the two amino acids 

 in the molecule are the same. It can be calculated from the number of 

 asymmetric carbon atoms in the molecule just as in the open chain 

 compounds ; thus alanyl-leucine anhydride can exist in four optically 

 active forms and two racemic forms : 



1. d-alanyl-d-leucine anhydride ; 



2. d-alanyl-1-leucine 



3. 1-alanyl-d-leucine 



4. 1-alanyl-l-leucine 



5. a mixture of I and 4 ; 



6. a mixture of 2 and 3. 



The same diketopiperazines are obtainable either from the dipep- 

 tides alanyl-leucine or from the dipeptides leucyl-alanine, so that in 

 fact the number of isomers of a diketopiperazine composed of two 

 different amino acids is less than those of the isomers of the dipeptide 

 composed of the same two amino acids. 



At present only a racemic form prepared from leucyl-alanine by 

 fusion has been obtained ; its nature has not yet been determined. 



