INTRODUCTION 7 



known and it only admits of the chain being lengthened in one direc- 

 tion, namely on the side of the amino group. 



3. It was of very great importance to be able to lengthen the chain 

 on the side of the carboxyl group. This is possible only by means of 

 the acid chloride of the amino acid. At the commencement of Fischer's 

 work the acid chlorides of the amino acids were unknown, but it was 

 discovered that the acid chloride of the halogen acyl derivative of an 

 amino acid could be prepared ; these compounds react with the esters 

 of amino acids in the following way : 



chloracetyl-glycyl chloride + alanine ester give chloracetyl-glycyl-alanine ester. 



Subsequent hydrolysis of the ester and treatment with ammonia gives 

 the tripeptide. 



Higher polypeptides are formed if esters of the di-, tri-peptides 

 are used in the place of the amino acid ester. 



Fischer ultimately succeeded in preparing the acid chlorides of the 

 amino acids so that any possible combination of the amino acids can 

 now be made by this method. 



These methods have been used for the synthesis of several 

 higher polypeptides, such as two hexapeptides, a heptapeptide, an 

 octapeptide, a dodecapeptide and even an octadecapeptide which 

 contains eighteen amino acid radicles combined together. They con- 

 sist principally of glycyl radicles ; the dodecapeptide contains eleven 

 glycyl radicles and one leucyl radicle ; the octadecapeptide fifteen 

 glycyl radicles and three leucyl radicles. Though such long chains 

 composed of glycine probably do not exist in a natural protein, with 

 perhaps the exception of gelatin which contains about 20 per cent of 

 glycine, their preparation has shown the possibilities of synthesis by 

 these methods. 



Glycine was used as unit in these complex substances partly 

 because it can be obtained easily, and partly because stereoisomeric 

 compounds cannot occur in these synthetical compounds. Glycine is 

 readily prepared by synthesis ; this is not the case with most of the 

 other amino acids, many of which are most easily obtained by the 

 hydrolysis of proteins. Glycine is optically inactive and is used in 

 preference to the racemic amino acids since four stereoisomeric forms 

 of a dipeptide containing optically active units can exist and the 

 number is greater as the length of the chain increases. 



Up to the present time over two hundred polypeptides have been 

 synthesised, and a great number of the simpler ones consist entirely of 

 optically active units. 



