THE CHEMICAL CONSTITUTION OF THE UNITS 125 



D. HETEROCYCLIC COMPOUNDS. 

 Histidine. 



Histidine was discovered in 1896 by Kossel amongst the decom- 

 position products of sturine, the protamine obtained from the ripe testis 

 of the sturgeon. In the same year Hedin isolated a base from the 

 products of hydrolysis of various proteins, which he regarded as identical 

 with Kossel's histidine, and this was subsequently shown to be the 

 case by Kossel and Kutscher. Kutscher also found it in antipeptone 

 obtained by the pancreatic digestion of fibrin, and Schulze and Winter- 

 stein have shown that it occurs as a decomposition product of various 

 vegetable proteins. Its presence in thyreoglobulin was shown by Koch. 



Histidine was found to possess the formula C 6 H 9 N 3 O 2 , but beyond 

 the facts that it formed a dichloride, that two of its hydrogen atoms were 

 replaceable by metals and that it was optically active and therefore 

 contained an asymmetric carbon atom, no experiments to determine its 

 constitution were published until 1903. Herzog then showed that it 

 gave the biuret reaction on warming, that it did not contain a methyl 

 nor a methoxyl group, and that it was very resistant to oxidising re- 

 agents and, in fact, behaved as a saturated compound. At the same 

 time Frankel showed that it contained a carboxyl group and an amino 

 group, which was replaced by the hydroxyl group by the action of 

 nitrous acid ; it was therefore (NH 2 ) . C 5 H 6 N 2 . COOH. As it gave 

 Weidel's pyrimidine reaction and did not contain a pyrrole ring nor a 

 guanidine group, Frankel suggested that it might be a derivative of 

 dihydropyrimidine, 



HN CH 2 HN CH 2 



either H.C C.CH 2 NH 2 or CH S .C C.NH 2 



N C COOH N C COOH 



but Weigert pointed out that neither of these formulae possessed an 

 asymmetric carbon atom, and that histidine was optically active ; con- 

 sequently its formula must remain as (NH 2 ). C 6 H 6 N 2 . COOH. 



Pauly, in 1904, confirmed the presence of a carboxyl group, and 

 showed that histidine contained a secondary amine group as well as a 

 primary amine group by preparing a dinaphthalene sulphonyl deriva- 

 tive, the remaining nitrogen atom being probably a tertiary one. He 

 pointed out that the resistance of histidine to oxidation and to acid per- 

 manganate, and that the formation of a di-silver compound were against 

 the presence of a dihydropyrimidine ring in its molecule. These proper- 

 ties, as well as the capability which histidine possessed of forming azo- 

 dyes with diazonium salts, pointed to the existence of a glyoxaline or 



