THE SYNTHESIS OF THE PROTEINS 33 



amino acid chlorides, so that he was enabled to combine together any 

 two amino acids in any order, without the necessity of preparing the 

 corresponding halogen derivative. Polypeptides containing the natural 

 optically active amino acids can thus be synthesised with ease, since the 

 natural compound obtained by hydrolysis can be again used directly 

 in the synthesis, and very often it is easier to prepare the natural 

 compound than the synthetical one, which also requires separation into 

 its stereoisomers. 



The synthesis of polypeptides composed of different amino acids is 

 most easily effected by this method. Those containing tyrosine are of 

 particular interest, since the first natural tetrapeptide was isolated from 

 silk in 1907, and was composed of glycine, alanine and tyrosine. 

 Twelve isomers are possible for a tetrapeptide, of this composition, 

 but if the results of partial hydrolysis and subsequent anhydride forma- 

 tion be taken into account, this number is reduced to eight. Of these, 

 glycyl-d-alanyl-glycyl-1- tyrosine was synthesised in 1908 by combining 

 chloracetyl-d-alanyl-glycylchloride with 1-tyrosine ester : 



Cl . CH 3 . CO NH . CH(CH 3 ) . CO NH . CH 2 . COC1 + 2NH 2 . CH(C 6 H 4 OH) . COOCH, 

 = HC1 . NH 2 . CH(C 6 H 4 OH) . COOCH 3 + Cl . CH 2 . CO NH . CH(CH ') .CO ' 

 NH . CH 2 . CO NH . CH(C 6 H 4 OH) . COOCH 3 



saponifying the resulting chloro compound with caustic soda and 

 treating with aqueous ammonia : 



Cl . CH 2 . CO NH . CH(CH 3 ) . CO NH . CH, . CO NH . CH(C 6 H 4 OH) . COOCH, + 



H 2 + aNH, = CH 3 OH + NH 4 C1 + NH 2 . CH 2 . CO NH . CH(CH 3 ) . CO 



NH . CH 2 . CO NH . CH(C 6 H 4 OH) . COOH 



This product, though it had many points of resemblance, such as 

 precipitation by phosphotungstic acid, tannic acid, hydrolysis by tryp- 

 sin, with the natural tetrapeptide, was not, however, identical with it ; 

 it differed mainly in its behaviour to ammonium sulphate, by which it 

 was only salted out with great difficulty. 



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. 



The accompanying table gives a list of the compounds prepared by 

 this method. 



PT. II. 



