30 THE CHEMICAL CONSTITUTION OF THE PROTEINS 



///. Synthesis of Polypeptides by Means of the Acid Chlorides of the 

 Amino Acids and of the Polypeptides. 



This, the simplest method of combining together two or more amino 

 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 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 carbethoxyl 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-glycy] 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 contains 

 four glycyl groups, and was the first known representative of the tetra- 

 peptides. 



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 saponification 

 with soda, the free acid, but the preparation of the simple polypeptide 

 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 poly- 

 peptides, e.g. 



Bromisocapronylglycine was converted into its acid chloride and 



