132 THE CHEMICAL CONSTITUTION OF THE PROTEINS 



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 pyrrolidone carboxylic 

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

 acid. 



Leuchs, in 1905, synthesised two stereoisomeric-fy-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, 



COOC 2 H 6 CH 2 CH 8 CH(COOC 4 H B ) 2 



:HNa + O CH CH 2 C1 = CH 2 C1 . CHOH 



COOC 2 H 5 



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

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



COOC 2 H 5 



CH CH 2 CH.CH 2 C1 



io i 



This compound on bromination, followed by hydrolysis of the ester 

 group with hydrobromic acid and removal of carbon dioxide, gave 

 <x-brom-8-chlor-7-valerolactone, from which by treatment with ammonia 

 7-oxyproline was obtained : 



COOC 2 H 5 COOH H 



CBr.CHj.CH.CH^l -> CBr. CH,. CH . CH 2 C1 -> CBr . CH 2 . CH . CH 2 C1 -> 



CO- O CO O CO O 



CH(NH 2 ) . CH 2 . CH . CH 2 NH 2 NH 



CO O CH 2 CH . COOH 



CHOH CH 



As this compound contains two asymmetric carbon atoms, four 

 stereoisomeric forms are possible ; by synthesis these must occur in two 

 inactive forms. These forms Leuchs separated by crystallisation of 

 the copper salts, the more insoluble acid being termed (a)-7-oxyproline, 

 the other (b)-7-oxy pro line. 



The constitution of these acids was confirmed in 1908 by Leuchs 

 and Felser, who converted them, by reduction with hydriodic acid, into 

 proline. Their attempt to determine whether natural oxyproline was 



