38 THE CHEMICAL CONSTITUTION OF THE PROTEINS 



Method HI. By Means of the Acid Chlorides of the Amino 

 Acids and of the Polypeptides. 



This, the simplest method of combining together two or moreamino 

 acids, is the one, in contradistinction to the previous one, by which the 

 chain of amino acids can be lengthened at the carboxyl end of the 

 molecule. It could not be employed at the commencement of Emil 

 Fischer's researches, since the l acid chlorides of the amino acids were 

 unknown, and all attempts to prepare them had failed ; but it is now 

 of the greatest importance, as it admits of the preparation of any con- 

 ceivable polypeptide, and it has also given us the knowledge of the 

 most complex compound known by synthesis. 



Although the acid chlorides of the amino acids themselves were 

 unknown, it was found by Fischer that their car bethoxyl derivatives, 

 as also those of the dipeptides which had been prepared, could be con- 

 verted into their acid chlorides by the action of thionyl chloride, and 

 that these compounds could be combined with the esters of the amino 

 acids or of polypeptides, thus : 



Carbethoxyl-glycyl chloride and glycine ester yielded carbethoxyl-glycyl-glycine ester. 



Carbethoxyl-glycyl chloride and glycyl -glycine ester yielded carbethoxyl-diglycyl-glycine 

 ester. 



Carbethoxyl-glycyl-glycyl chloride and glycyl-glycine ester yielded carbethoxyl-triglycyl- 

 glycine ester. 



This last compound on hydrolysis gave the free acid, which con- 

 tains four glycyl groups, and was the first known representative of the 

 tetrapeptides. 



In the same way derivatives of mixed polypeptides could be ob- 

 tained, e.g., carbethoxyl-glycyl-alanine ester. From it, by the action 

 of ammonia, Fischer and Otto prepared the amide and, by saponifica- 

 tion with soda, the free acid, but the preparation of the simple poly- 

 peptide could not be effected, since it was impossible to remove the 

 carbethoxyl group without complete destruction of the molecule. 



In 1904 Fischer found that the presence of a halogen acyl group 

 in the molecule of an amino acid again allowed of the preparation of 

 the acid chloride, i.e., when the amino group of the amino acid was 

 rendered stable, and that this compound was formed by the action of 

 phosphorus pentachloride in the presence of acetyl chloride. As before, 

 this acid chloride could be combined with the esters of amino acids or 

 of polypeptides, e.g. 



Bromisocapronylglycine was converted into its acid chloride and 



