10022-82-9

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Mixtures of carbohydrate decomposition products and L-tryptophan were incubated at pH 7.0 and 37°C for 4 weeks. These mixtures exhibited mutagenic activity toward S. typhimurium TA 100 without metabolic activation after a nitrite treatment at pH 4.0. Four β-carboline derivatives were isolated as premutagens from mixtures of methylglyoxal and furfural. These premutagens were also found to be contained in daily foodstuffs and human urine samples.

Motivated by the identification of numerous novel tetrahydro-β-carboline-carboxylic acids in food samples, we studied the reactions of tetrahydro-β-carbolines in the presence of nitrosating agents. The anticipated formation of nitroso derivatives from unsubstituted tetrahydro-β-carbolines, and from tetrahydro-β-carboline-3-carboxylic acids was indicated by HPLC-MS/MS analysis and validated by the characteristic product ion spectra of the respective nitroso compounds. In addition, oxidative decarboxylation resulted in formation of the corresponding dihydro-β-carbolines, and in the generation of the β-carbolines harman or norharman. Subsequently, we studied the reactivity of tetrahydro-β-carboline-1-carboxylic acids derived from the Pictet-Spengler condensation of indole amines with α-oxo acids. Again, in the presence of nitrosating agents the rapid disappearance of the starting material was obvious, but no nitroso derivatives could be observed. Instead, further HPLC-MS/MS studies demonstrated that dihydro-β-carbolines were the major products of tetrahydro-β-carboline-1-carboxylic acids. Finally, we demonstrated that freshly isolated nitroso-precursors spontaneously decomposed to yield harman alkaloids. In conclusion, we revealed that nitroso-tetrahydro-β-carbolines can represent intermediates involved in the generation of β-carbolines, and we established a novel pathway for the formation of harman alkaloids from nutritional tetrahydro-β-carbolines.

A series of β-carboline derivatives were synthesized by utilizing aromatization and chemoselective alkylation method recently reported from our laboratory. Synthesized derivatives were evaluated for anti-HIV activity in human CD4+ T cell line (CEM-GFP) infected with HIV-1 NL4.3 virus. 1-Formyl-β-carboline-3-carbxylic acid methyl ester (15) showed inhibition of human immunodeficiency virus at IC50 = 2.9 μM.

Unprecedented aromatization was observed during N-alkylation reactions of 1-methyl-3,4-dihydro-β-carboline-3-carboxylic acid methyl ester, giving rise to 9-alkyl-1-methyl-β-carboline-3-carboxylic acid methyl esters. Inverse addition of base during a simil

C-terminal tryptophan containing peptides have been converted into 1-peptidyl-3,4-dihydro-β-carboline-3-carboxylic acids by acid catalyzed isomerization of their azlactone derivatives. The main properties of these abnormal peptides are a strong absorption around 360 nm an intense fluoroscence and ability to generate reactive carbanions when dissolved in basic media. This tryptophan conversion takes place with high yield and is of general applicability.