Harman carboxylic acid

Sanchez and Brown have obtained a new harman derivative from Aspi-dosperma exalatum Monachino (121). The alkaloid was obtained from a butanol extract, and in the IR spectrum it showed principal absorptions at 1925 cm-1 for an immonium ion, at 1610 cm-1 for a carboxylate anion, and at 748 cm-1 for a disubstituted benzene. In the mass spectrum a molecular ion was observed at m/e 226 and a base peak at m/e 182 (M+ —44). An aromatic methyl group and five aromatic protons were observed in the PMR spectrum. Consideration of this data together with the UV spectrum led to deduction of the structure of the alkaloid as 268, harman carboxylic acid. The ethyl ester (269) was also isolated but it was probably an artifact. 

For the preparation of 3,4-dihydro-/3-carbolines the Bischler-Napieralski reaction is widely used (510R74). Since this reaction requires rather drastic conditions, A-acetyl tryptophan and its analogs yielded l-methyl-/8-carboline (harman) rather than l-methyl-3,3-dihydro-j8-carboline-3-carboxylic acid derivatives owing to accompanying decarboxylation and aromatization (41JCS153 50JA2962). 

DBC 34 (harmalan) is a rare mammalian alkaloid present in goat urine (67). The fully aromatic BC 35 (norharman), on the other hand, is an endogenous metabolite in man (44), and BC 36 (harman) was found to be present in tissues of rat and man (1,46,54,68,69). Carboxylic acid 37 was detected in cerebral fluids of monkeys (70), and analog 38 was detected in bovine milk and urine (71). 

Harman-3-carboxylic acid (268) Aspidosperma exalatum (121) 300 — (121) 226 C13HI0N2O2... 

Leonard and Elderfield have also carried out degradation experiments with alstonine and its tetrahydride. On fusion with potassium hydroxide at 300-350° in nitrogen, alstonine furnishes harman (p. 490) and indefinite basic and acidic fractions. Tetrahydroalstonine on like treatment produces harman, norharman, and three unidentified bases, each of which fluoresces blue in alcoholic hydrochloric acid Base A, m.p. 171-5 to 172-5°, forms a picrate, m.p. > 267° is probably a substituted -carboline. Base B, CieH e or 18 2) gives a picrate, m.p. 261° (dec.). Base C, isolated as the picrate, m.p. 203-5-205-5°. From the acid products of the fusion indole-2-carboxylic acid was isolated. 

Decarboxylation and oxidation products of 1,2,3,4-tetrahydro-P-carbohne-3-carboxylic acids derived from formaldehyde, 9H-pyrido(3,4-fo]indole (norharmane, 2-127), and acetaldehyde, 1-methyl-9//-pyrido[3,4-fo]indole (harmane, 2-127), were identified in a number of foods at levels up to 700 mg/kg, although more typically their concentrations in smoked, cooked and fermented foods range from a few mg/kg to 1-2 orders of magnitude less. Typical norharmane and harmane findings in pan-fried, minced meat, beef patties or ground beef prepared at temperatures of 175-230 °C and... 

Although a great number of alkaloids having a /8-carboline structure have been found in nature, very few reports have been published about their biogenesis, and these are concerned only with the plant material. From among the alkaloids mentioned above only harman (180) and 4,5-dihydrocanthin-6-one (181) were demonstrated in feeding experiments with H- and C-labeled precursors to be derived biosynthetically from tryptophan. In the case of harman, tryptamine is probably condensed with pyruvic acid to give l-methyl-l,2,3,4-tetrahydro-j8-carboline-l-carboxylic... 

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