42 THE CHEMICAL CONSTITUTION OF THE PROTEINS 



the further products : the glycyl-tyrosyl-glycyl-alanine though active 

 is probably a mixture of two stereoisomers. 



Formyl tyrosine can also be used in the syntheses by this method 

 after combination with methyl or ethyl chlorocarbonate. 



Polypeptides containing tyrosine are of the greatest interest, since 

 the first natural tetrapeptide was isolated from silk in 1907 and was 

 composed of two molecules of glycine, one molecule of alanine and one 

 molecule of tyrosine ; and it behaved like the secondary proteoses with 

 ammonium sulphate. Twelve isomers are possible for a tetrapeptide 

 of this composition ; this number is reduced to eight if the results of 

 partial hydrolysis and subsequent anhydride formation be taken into 

 account (p. 82). Of these, the synthesis of glycyl-tyrosyl-glycyl-alanine 

 has just been described ; glycyl-d-alanyl-glycyl-1-tyrosine was syn- 

 thesised in 1 908 by combining chloracetyl-d-alanyl-glycyl chloride with 

 1-tyrosine ester : 



Cl.CHj.CO NH.CH(CH,).CO NH.CH 2 .COCl + 2NH,.CH.CH a (C 9 H 4 OH).COOCH I 



= HC1 .NH, . CH . CH a (C 6 H 4 OH) . COOCH, + 

 Cl . CH,. CO NH . CH(CH,) . CO NH . CH, . CO NH . CH . CH,(C 6 H 4 OH) . COOCHj 



saponifying the resulting chloro compound with caustic soda and treat- 

 ing with aqueous ammonia : 



CI . CH, . CO NH . CH(CHj) . CO NH . CH, . CO NH . CH . CH,(C 8 H 4 OH) . COOCH, 



+ H,O + 2NH 3 = CHjOH 4- NH 4 C1 + 

 NH, . CH, . CO NH . CH(CH,) . CO NH . CH,. CO NH . CH . CH 8 (C 6 H 4 OH) . COOH 



This product, though it had many points of resemblance with the 

 natural tetrapeptide, such as precipitation by phosphotungstic acid, 

 tannic acid, hydrolysis by trypsin, was not identical with it ; it differed 

 mainly in its behaviour to ammonium sulphate, by which it was only 

 salted out with great difficulty ; the first compound showed closer 

 relationship to the proteoses with ammonium sulphate. 



An attempt was made at the same time to prepare the isomeric 

 d-alanyl-glycyl-glycyl-1-tyrosine ; it failed on account of the difficulty 

 of preparing pure a-bromopropionyl-glycyl-glycyl chloride, but there 

 seems no reason to suppose that Fischer will not overcome this small 

 difficulty in preparing a desired compound, when he has overcome such 

 vast difficulties already in connection with the synthesis of the poly- 

 peptides. 



This method is most useful in the synthesis of those polypeptides 

 containing amino acids having no corresponding halogen derivative 

 of easy access, e.g., tryptophane, proline. Abderhalden has prepared 

 1-tryptophyl-glutamic acid and 1-leucyl-l-tryptophyl-glutamic acid. 



