64 THE CHEMICAL CONSTITUTION OF THE PROTEINS 



There was no difficulty in identifying the natural substance with the 

 synthetical one, and its presence in egg-albumin, gelatin and other pro- 

 teins was soon afterwards established. 



The question at once arose whether this a-pyrrolidine carboxylic acid, 

 or a-proline as Fischer termed it in 1904, was a primary product or a 

 secondary product formed by the action of mineral acids upon other 

 products, but its formation by hydrolysis by alkali and by the action of 

 pepsin followed by trypsin decided that it was a primary product and 

 therefore one of the units of the protein molecule. Sorensen, in 1905, 

 suggested that it might arise from an a-amino-S-oxyvalerianic acid 

 which he synthesised, but the fact that this amino acid has not yet been 

 obtained by hydrolysis of protein and the above facts seem to exclude 

 this possibility. 



Oxyproline. 



In 1902 E. Fischer isolated a compound of the empirical formula 

 C 5 H 9 O 3 N from the hydrolysis products of gelatin. From its composi- 

 tion he supposed that it was an oxy-derivative of pyrrolidine carboxylic 

 acid, and this was proved by its reduction to proline with hydriodic 

 acid. 



Leuchs, in 1905, synthesised two stereoisomeric-y-oxy-prolines, one 

 of which is probably the inactive form of the natural oxyproline. 

 Epichlorhydrin and sodium malonic ester yield 7-chlor-/3-oxy-propyl- 

 malonic ester, 



CH 2 CH 2 CH(COOC 2 H 5 ) 2 



CHNa + O CH CH 2 C1 = CH 2 C1 . CHOH 

 >C 2 H 5 



COO( 



which loses alcohol and is converted into its lactone, i.e., the ester of 

 S-chlor-7-valerolactone-a-carboxylic acid, 



COOC 2 H 5 



CH CH 2 CH.CH 2 C1 



CO O 



This compound on bromination, followed by hydrolysis of the ester 

 group with hydrobromic acid and removal of carbon dioxide, gave 

 a-brom-S-chlor-y-valerolactone, from which by treatment with ammonia 

 7-oxyproline was obtained : 



