Kynurenic acid structure

It was only many years after the discovery of tryptophan that a plausible degradative pathway could first be outlined, but during this early period a few tryptophan metabolites were identified. The long-known (559) kynurenic acid (structure, diagram 20 cf. 408) was shown in 1904 to be derived from tryptophan (220), but the considerable amount of work on kynurenic acid formation (reviewed by Neubauer, 637) gave few useful results. Neubauer (637), however, made the plausible (and correct) suggestion that it was derived from o-aminobenzoylpyruvic acid (structure, diagram 20). 

Glycines site antagonists which have been shown to be effective in analgesic models can be divided into different chemical classes although so far any high affinity effector molecule of the glycineB site bears more or less the structural motif of glycine within its molecular structure, as can be observed in the first example, kynurenic acid. 

Chlorokynurenic acid 5,7-Dichlorokynurenic acid Scheme 3 Structures of kynurenic acid derivatives. 

In spite of laborious work, knowledge of the mechanism and of the possible intermediates of the pathway tryptophan —> kynurenic acid made little progress until the isolation of kynurenine (M4). This compound, whose structure (o-aminobenzoylalanine) became clear only many years later (B26), is the intermediate (as shown by S. Kotake), no longer an indole, between tryptophan and kynurenic acid (K12). 

A plausible hypothesis at this stage (about 1943) was that a sequence occurred tryptophan —> an intermediate kynurenine kynurenic acid. It was thought that the intermediate between tryptophan and kynurenine might be the so-called a-hydroxytryptophan (for structure see p. 83), which had been obtained (917) on hydrolysis of phalloidine, a toxic peptide from the fungus Amanita pkalloides (567) such a pathway received... 

Our knowledge of tryptophan began some 100 years ago. In 1901 Hopkins and Cole1 isolated tryptophan from a pancreatic digest of casein. Its structure was established in 1907 by Ellinger and Flamand,2 who synthesized a substance that was identical to the tryptophan isolated by Hopkins and Cole. It is noteworthy that about 50 years prior to the discovery of tryptophan by Hopkins and Cole,1 aspects of tryptophan metabolism began to appear in the research literature, when in 1853 Liebig discovered kynurenic acid in dog urine.3 Subsequently, kynurenine, a tryptophan metabolite, was identified,4 5 and the relationship of kynurenic acid to tryptophan was understood. A brief review on the discovery of tryptophan has been described by Curzon.6... 

Kynurenic acid was discovered in 1853 by Liebig and has been isolated from the urine of many mammalian species. It was shown to be a metabolic product of tryptophan by Ellinger by feeding tryptophan to rats. He also proposed a structural formula for it which, however, was not quite correct. 

The correct structure was established by Homer. Kynurenic acid is formed from L-tryptophan and from indolepyruvic acid, but not from the D-amino acid. ... 

Tryptophan is among the most interesting aminoacids because its biologic role goes far beyond its participation in proteins structure. In mammals, tryptophan is the precursor in the synthesis of the neurotransmitters tryp-tamine and serotonine, as well as of other bioactive molecules such as kynurenic and quinolinic acids. Along with the usual catabolic pathway of the aminoacid, other essential compounds are found, such as nicotinic acid and melatonin [1-3]. 

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