60 SECTIONAL ADDRESSES. 



and the question is which of the two nitrogen atoms of tryptophane 

 survives. Is the pyrrole ring enlarged to a pyridine ring, as when indole 

 is treated with chloroform and alkali, or is the pyrrole ring oxidised and 

 does the pyridine ring arise from the side chain of tryptophane ? It is 

 almost certain that the latter alternative holds good. 



In 1914 Ellinger and Matsuoka synthesised Pr-2. methyltryptophane, 

 but could not obtain any methylkynurenic acid from it ; and having 

 overlooked their publication, Ewins and I a few years afterwards made 

 the same amino-acid, and obtained the same negative result. Later in 

 Edinburgh I suggested to Dr. W. Robson the synthesis of a trytophane 

 with a methyl group in the benzene nucleus, which would not interfere 

 with the oxidation of the pyrrole ring. He synthesised Bz-3. methyl- 

 tryptophane and also 6-methyl and 8-methylkynurenic acids, which might 

 be expected to be formed from it according to the two rival theories : 



COH 



X\ I II I 



Me I ]| |(CH,CH(NH,)COOH ^ \// \/C.COOH 



Theory 1 ^,-^— "^ N 



NH 



Bz-3. methyltryptophane ^-^ 6-methylkynuremc acid 



Theory n\,^^ 



N=C.COOH 

 ^^ / >CH 



-COH 



/\. ^ 



S-methylkynurenic acid 



Even this very considerable expenditure of organic chemical effort 

 did not absolutely settle the matter, for the Bz methyltryptophane did 

 not yield any kynurenic acid either. Robson found, however, that 

 6-methylkynurenic acid passes through the body unchanged, whereas 

 8-methylkynurenic acid is completely burnt. It is therefore likely that 

 it is formed from Bz-3. methyltryptophane as a transitory intermediate 

 product, for if 6-methylkynurenic acid were formed, the latter would 

 resist oxidation. Robson concluded therefore, that the single nitrogen 

 atom of kynurenic acid is the one from the side chain of tryptophane 

 {Theory II). Ellinger and Matsuoka, in 1920, after obtaining kynurenic 

 acid from indole pyruvic acid, concluded that the pyrrole ring is indeed 

 opened up, but that its nitrogen atom ultimately survives in kynurenic 

 acid (Theory I). The weakness in the latter's reasoning is that indole 

 pyruvic acid might conceivably be converted in the body into tryptophane, 

 and may not yield kynurenic acid directly. 



The example of kynurenic acid will serve to show that there is scope 

 for the application of organic chemistry to the problems of intermediate 

 metabolism, and also the difficulties involved in drawing definite con- 

 clusions. 



The first stage in the degradation of fatty acids and of amino-acids 



