Pyrrole-2,3,5-tricarboxylic acid

There are no reports in the literature of the formation of pyrrole derivatives by the oxidative degradation of the o-quinone rings of the simple aminochromes. However, several pyrrolecarboxylic acids have been obtained on oxidation of the melanins, which are considered by some authors to contain aminochrome units in the polymer (cf. ref. 168), (see Section V, A), and pyrrole-2,3,5-tricarboxylic acid has been... 

The aglycone of betaniu, the red-violet pigment of the beet (Beta vulgaris var. rubra), known as betanidin, has recently been shown to have the structure depicted in structural formula 113.170,282 Betanidin had previously been reported by Piattelli and Minale to contain a dopachrome unit in its structure and consequently would have been formulated as 114.109 The Italian workers obtained pyrrole-2,3,5-tricarboxylic acid and pyridine-2,4,6-tricarboxylic acid on permanganate oxidation of betanidin and they also prepared a semi-carbazone of the pigment, the absorption spectrum of which showed the pH dependency expected for an aminochrome semicarbazone.169... 

Permanganate oxidation of eumelanins yields pyrrole-2,3,5-tricarboxylic acid, while HI hydrolysis of III... 

Skaddan and co-workers employed the Hantzsch synthesis in their preparation of isotopically labeled l- -pyrrole-2,3,5-tricarboxylic acid, a metabolic by-product of the breakdown of melatonin. Labeled -H-pyrrole-2,3,5-tricarboxylic acid is currently under investigation as a tool to study the effectiveness of new hyper pigmentation drugs. C-Labeled ethyl acetoacetate 19 and 2-chloroethanal 20, when treated with -labeled aqueous ammonium hydroxide, produced pyrrole 21 in 35% yield. The authors chose to use this approach due to the relatively low cost and availability of the reagents required to prepare this compound. 

The large scale preparation of orthogonally protected pyrrole tricarboxylic acid derivatives (i.e., 92) was reported. A key step was the selective a-chlorination of a 2,4-dimethylpyrrole intermediate that was derived from the Knorr pyrrole synthesis. 

Knorr reported the first pyrazole derivative in 1883. The reaction of phenyl hydrazine and ethylacetoacetate resulted in a novel stmcture identified in 1887 as l-phenyl-3-methy 1-5-pyrazolone 9. His interest in antipyretic compounds led him to test these derivatives for antipyretic activity which led to the discovery of antipyrine 10. He introduced the name pyrazole for these compounds to denote that the nucleus was derived from the pyrrole by replacement of a carbon with a nitrogen. He subsequnently prepared many pyrazole analogs, particularly compounds derived from the readily available phenyl hydrazine. The unsubstituted pyrazole wasn t prepared until 1889 by decarboxylation of liT-pyrazole-3,4,5-tricarboxylic acid. ... 

PQQ (methoxatin 4,5-dihydro-4,5-dioxo-lH-pyrrolo [2,3-f] quinoline-2,7, 9-tricarboxylic acid), 2-(dimethylamino) ethanethiol (DMAET), 2-(diethylamino) ethanethiol (DEAET), and pyrrole were purchased from Sigma (St. Louis, MO). Potassium hydrogen phthalate was purchased from Acros (Pittsburgh, PA). Pyrrole was distilled every time immediately before use. All other regents were used without further purification. 

The total synthesis of (+ )-dehydroheliotridine (4), a toxic metabolite of the pyrrolizidine alkaloids (e.g. lasiocarpine and heliotrine), has also been described.2 The pyrrole ring was obtained by reaction of l,6-dihydroxy-2,5-dicyanohexa-l,3,5-triene-l,6-dicarboxylic ester (5) with j3-alanine, which afforded the N-substituted pyrrole ester (6), together with the appropriate amide of oxalic acid. Careful hydrolysis of (6) with dilute alkali afforded the related tricarboxylic acid, which was converted, by Dieckmann cyclization, hydrolysis and decarboxylation, into the keto-acid (7). Esterification of (7) with diazomethane, followed by reduction with lithium aluminium hydride, finally afforded ( )-dehydroheliotridine (4), identical, except in optical rotation, with dehydroheliotridine obtained earlier by Culvenor et al.3... 

Oxidation of sepiomelanin with potassium permanganate gave four pyrrolic acids, pyrrole-2,3,5- and 2,3,4-tricarboxylic acid, pyrrole-2,3-dicarboxylic acid (PDCA), and 2,3,4,5-pyrroletetracarboxylic acid (184, 204). On the other hand, the yield and number of PDCA increased when decarboxylated sepiomelanin was oxidized with permanganate. The origin of these pyrrolic acids was interpreted as resulting from the oxidative breakdown of various types of DHI units in the pigment backbone (184). 

The Knorr pyrrole synthesis was also employed for the synthesis of 3-trifluoropyrroles [91]. Treatment of ethyl trifluoroacetoacetate 267 with sodium nitrite in acetic acid led to the oxime 268. Refluxing with zinc dust and addition of 1,3-dicarbonyl compounds 269 afforded the 3-trifluoromethylpyrroles 270 in moderate yields. Using more acidic trifluoroacetic acid allowed to lower the reaction temperature to 70 °C [92]. Using a similar approach, the tricarboxylic acid ester 273 was prepared starting from the acetone dicarboxylic acid ester 271 and the fluorinated keto ester 272 [93]. 

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