Unsubstituted Indole Research Articles

L-tryptophan 2',3'-oxidase from Chromobacterium violaceum. Substrate specificity and mechanistic implications.

L-Tryptophan 2',3'-oxidase, an amino acid alpha,beta-dehydrogenase isolated from Chromobacterium violaceum, catalyzes the formation of a double bond between the C alpha and C beta carbons of various tryptophan derivatives provided that they possess: (i) a L-enantiomeric configuration, (ii) an alpha-carbonyl group, and (iii) an unsubstituted and unmodified indole nucleus. Kinetic parameters were evaluated for a series of tryptophan analogues, providing information on the contribution of each chemical group to substrate binding. The stereochemistry of the dehydro product was determined to be a Z-configuration from proton nuclear magnetic resonance assignments. No reaction can be observed in the presence of other aromatic beta-substituted alanyl residues which behave neither as substrates nor as inhibitors and therefore do not compete against this reaction. The enzymatic synthesis of alpha,beta-dehydrotryptophanyl peptides from 5 to 24 residues was successfully achieved without side product formation, irrespective of the position of the tryptophan residue in the amino acid sequence. A reactional mechanism involving a direct alpha,beta-dehydrogenation of the tryptophan side chain is proposed.

Tryptophan analogues form adducts by cooperative reaction with aldehydes and alcohols or with aldehydes alone: possible role in ethanol toxicity.

Previous work showed that the exocyclic amino groups of nucleic acid components react quickly at ambient temperature with acetaldehyde and ethanol to yield mixed acetals [R-NH-CH(CH3)-O-C2H5]. We now find that the same type of reaction occurs readily with the nitrogen of 3-substituted indoles (e.g., indole-3-acetic acid and N-acetyltryptophan), analogues of the amino acid tryptophan. In contrast, unsubstituted indole reacts very rapidly at the carbon in ring position 2 or 3 with acetaldehyde to form bis(indolyl)ethane without ethanol entering into the reaction. Product structures have been confirmed by fast atom bombardment MS and 1H NMR. The former reaction occurs optimally in 30-50% aqueous solution below pH 4. It also proceeds more slowly and with reduced yields in aqueous media at more neutral pH. This reaction may be of biological concern, as it supplies a mechanism for protein modifications with possible toxic effects in human tissues where ethanol is metabolized.

Specificity of dopachrome tautomerase and inhibition by carboxylated indoles. Considerations on the enzyme active site

Dopachrome tautomerase (EC 5.3.2.3) catalyses the tautomerization of dopachrome to 5,6-dihydroxyindole-2-carboxylic acid (DHICA) within the melanin-formation pathway. We have analysed a series of substrate analogues and related compounds as possible substrates and inhibitors of tautomerization. The enzyme appears to be highly specific since D-dopachrome, alpha-methyldopachrome, dopaminochrome, adrenochrome methyl ether and deoxyadrenochrome are not substrates. Conversely, dopachrome tautomerase catalyses the tautomerization of dopachrome methyl ester, suggesting that a carboxy group, either free or as a methyl ester, is essential for enzyme recognition. No inhibition of dopachrome tautomerization was observed in the presence of either semiquinonic compounds, such as tropolone and L-mimosine, or pyrrole-2-carboxylic acid and unsubstituted indole. However, a number of indole derivatives, including DHICA, the product of dopachrome tautomerization, and the analogues 5-hydroxyindole-2-carboxylic and indole-2-carboxylic acid were able to inhibit the enzyme. Furthermore, indoles with a side chain at position 3 of the ring and containing a carboxylic group at the gamma-position of this chain, such as L-tryptophan or indole-3-propionic acid, are stronger inhibitors of the enzyme. Indole-3-carboxylic acid, indole-3-acetic acid and indole-3-butyric acid are very weak inhibitors, showing that the carboxylic group needs to be located at an optimal distance from the indole ring to mimic the carboxylic group at position 2 on the authentic substrate.

Chemo‐enzymatic synthesis and characterization of L‐tryptophans selectively 13C‐enriched or hydroxylated in the six‐membered ring using transformed Escherichia coli cells

AbstractL‐(3a‐13C)‐ And L‐(6‐13C)tryptophan have been synthesized from simple labelled compounds via a single reaction scheme based on the conversion of 1,3‐cyclohexanedione into indole. The labelled indoles have been converted in one step into the corresponding L‐tryptophans using transformed Escherichia coli cells with large amounts of the enzyme, tryptophan synthetase. The same reaction scheme has been used for the synthesis of 4‐ and 7‐indolol. These hydroxyindoles together with 5‐indolol have been converted into 4‐, 7‐ and 5‐hydroxy‐L‐tryptophan, respectively, using the Escherichia coli cells. The latter compound is the immediate precursor of the neurotransmitter, serotonin. It appears that 7‐indolol is the only indole derivative which is converted faster than unsubstituted indole by the enzyme, tryptophan synthetase. With the preparation of L‐(3a‐13C)‐ and L‐(6‐13C)tryptophan, we have completed the series of indoles and L‐tryptophans with a stable isotope (13C, 15N or 2H) in the aromatic ring. In this paper, we also discuss the NMR parameters of these mono‐isotopically labelled systems.

Transient intermediates in intramolecularly photosensitized pyrimidine dimer splitting by indole derivatives.

Abstract— Intramolecularly photosensitized pyrimidine dimer splitting can serve as a model for some aspects of the monomerization of dimers in the enzyme‐substrate complex composed of a photolyase and UV‐damaged DNA. We studied compounds in which a pyrimidine dimer was covalently linked either to indole or to 5‐methoxyindole. Laser flash photolysis studies revealed that the normally observed photoejection of electrons from the indole or the 5‐methoxyindole to solvent was diminished by an order of magnitude for indoles with dimer attached (dimer‐indole and dimer‐methoxyindole). The fluorescence lifetime of dimer‐indole in aqueous methanol was 0.85 ns, whereas that of the corresponding indole without attached dimer (tryptophol) was 9.7 ns. Similar results were obtained for the dimer‐methoxyindole (0.53 ns) and 5‐methoxytryptophol (4.6 ns). The quantum yield of dimer splitting for the dimer‐methoxyindole (φ287K7 = 0.08) was only slightly greater than the value found earlier for the dimer bearing the unsubstituted indole (4>2K7= 0.04). Transient absorption spectroscopy also revealed lower yields of indole radical cations following laser flash photolysis of dimer‐indole compared to the indole without attached dimer. Dimer‐methoxyindole behaved similarly. These results are interpreted in terms of an enhanced rate of radiationless relaxation of the indole and methoxyindole excited singlet states in dimer‐indoles. The possible quenching of the indole and methoxyindole excited states via electron abstraction by the covalently linked dimer is discussed.

Copper catalysed phenylation of indoles by triphenylbismuth BIS-trifluoroacetate

Indoles are C(3)- or N-phenylated by triphenylbismuth bis-trifluoroacetate under copper catalysis. C(3)-Phenyl derivatives are obtained with C(3)- unsubstituted indoles and N-phenyl derivatives with C(3)-substituted indoles.

ChemInform Abstract: CYPRIDINA BIOLUMINESCENCE. X. SYNTHESIS AND CHEMILUMINESCENCE OF 2‐(INDOL‐3‐YL)‐3‐PHENYLDIHYDRO‐1,4‐DIOXIN 2,3‐EPIDIOXIDE, A DIOXETANE HAVING UNSUBSTITUTED INDOLE GROUP SIMILAR TO THE INTERMEDIATE PROPOSED IN CYPRIDINA BIOLUMINESCENCE

Chemischer InformationsdienstVolume 12, Issue 39 Heterocyclic Compounds ChemInform Abstract: CYPRIDINA BIOLUMINESCENCE. X. SYNTHESIS AND CHEMILUMINESCENCE OF 2-(INDOL-3-YL)-3-PHENYLDIHYDRO-1,4-DIOXIN 2,3-EPIDIOXIDE, A DIOXETANE HAVING UNSUBSTITUTED INDOLE GROUP SIMILAR TO THE INTERMEDIATE PROPOSED IN CYPRIDINA BIOLUMINESCENCE H. NAKAMURA, H. NAKAMURASearch for more papers by this authorT. GOTO, T. GOTOSearch for more papers by this author H. NAKAMURA, H. NAKAMURASearch for more papers by this authorT. GOTO, T. GOTOSearch for more papers by this author First published: September 29, 1981 https://doi.org/10.1002/chin.198139201AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume12, Issue39September 29, 1981 RelatedInformation

Reaction of indoles with trifluoroacetic acid

3-Trifluoroacetyl indoles are formed by the action of trifluoroacetic acid on indole-2-carboxylic acid and its benzo-substituted derivatives. When unsubstituted indole is refluxed with trifluoroacetic acid, it gives 3-trifluoroacetylindole in 30% yield.

Utilization of Indole Analogs by Carrot and Tobacco Cell Tryptophan Synthase in Vivo and in Vitro

Twenty-three indole analogs were used to inhibit the growth of carrot and tobacco suspension cultures. The addition of tryptophan or indole partially reversed the inhibition of both cell lines only for 4-fluoroindole, 5-fluoroindole, and 6-fluoroindole. Inhibition of tobacco cell growth by 5-aminoindole, 5-methoxyindole, 6-methoxyindole, or 7-methoxyindole was also partially reversed. Previously selected carrot and tobacco lines, which have high free tryptophan levels, grew in the presence of the analogs for which reversal was noted in all cases except 5-aminoindole and also in some other cases. Growth inhibition caused by all 10 tryptophan analogs studied was partially reversible by tryptophan or indole and the high tryptophan lines were also able to grow in the presence of concentrations inhibitory to the wild type lines.Tryptophan synthase activity from both species could utilize most of the 2 or 3 position unsubstituted indole analogs to produce the corresponding tryptophan analogs. Using carrot cell extracts, the identity of the correct product was confirmed by automated amino acid analysis for 4-fluoroindole, 5-fluoroindole, and 5-hydroxyindole. The analogs most rapidly utilized by carrot tryptophan synthase were 6-methoxyindole and the 4-, 5-, or 6-fluoroindoles. When 4-fluoroindole, 5-hydroxyindole, 5-methoxyindole, or 5-methylindole were incubated with carrot cells the corresponding tryptophan analog was formed in all cases as identified by amino acid analysis.These results indicate that cultured carrot and tobacco cells can convert certain nontoxic indole analogs into toxic tryptophan analogs. Using 5-fluoroindole and 6-fluoroindole, attempts were made to isolate tryptophan auxotrophs lacking tryptophan synthase from diploid carrot and tobacco lines. However, only 5-methyltryptophan-resistant lines, which presumably accumulate high levels of free tryptophan, were recovered.

Synthesis and Chemiluminescence of 2-(Indol-3-yl)-3-phenyldihydro-1,4-dioxin 2,3-Epidi-oxide, a Dioxetane Having Unsubstituted Indole Group Similar to the Intermediate Proposed in Cynpridina Bioluminescence

Synthesis and Chemiluminescence of 2-(Indol-3-yl)-3-phenyldihydro-1,4-dioxin 2,3-Epidi-oxide, a Dioxetane Having Unsubstituted Indole Group Similar to the Intermediate Proposed in Cynpridina Bioluminescence

Nachweis von indolalkylaminen nach selektiver derivatisierung

Determination of indolalkylamines after selective derivatisation The 1N-TMS- ωN-TFA-derivatives of indolalkylamines are suitable for estimation by combined gas chromatography and mass spectrometry for two reasons, viz. (1) Under electron impact charge stabilisation at the indole nucleus is favoured, so structure-specific ions form the base peak. For unsubstituted indoles m/e values of 202 are found and for hydroxyl-substituted indoles m/e values of 290. (2) The calibration curves of the derivatives are linear, even in the femtomole range. The 1N-TMS- ωN-derivatives can easily be obtained by trimethylsilylation with N-methyl-N-trimethylsilyltrifluoroacetamide containing catalytic amounts of N-trimethylsilylimidazole followed by acylation with N-methyl bis(trifluoroacetamide). The serotonin concentrations in different rat tissues are determined by this method of selective ωN-trifluoroacylation- 1N-trimethylsilylation and compared with the values obtained by pertrimethylsilylation. Die für den massenspezifischen Nachweis geeigneten ωN-TFA- 1N-TMS-Derivate der Indolalkylamine können mit N-Methyl-N-trimethylsilyltrifluoracetamid (MSTFA) als Silylierungsmittel und N-Methyl-bis(trifluoracetamid) (MBTFA) als Acylierungsmittel unter kontrolliertenn Reaktionsbedingungen als einheitliche Derivate erhalten werden. Zwei Massnahmen sind zur selektiven Derivatisierung erforderlich: (1) Die Verwendung von TMS-Imidazol als Katalysator zur raschen und vollständigen Trimethylsilylierung des indolylischen Protons. Die 1N-TMS-Gruppe ist stabil gegen den Einfluss von MBTFA. (2) Die Reduzierung des Silylierungspotentials im Reaktionsansatz. Unter den Bedingungen der Elektronenstossionisation zerfallen die 1N-TMS- ωN-TFA-Derivate unter Landungsstabilisierung am Indolkern. Zieht man die strukturspezifischen Ionen, wie das 1N-TMS-Chinoliniumion ( m/e 202) für unsubstituierte Indolalkylamine bzw. das 1N-TMS-O-TMS-hydroxychinoliumion ( m/e 290) für das ringsubstituierte Serotonin zum Nachweis heran, so erreicht man Nachweisgrenzen bis herab in den Femtomolbereich. Anwendungsbeispiele für die Bestimmung der Indolalkylamine werden gegeben, wobei ein Vergleich zur Pertrimethylsilylierung gezogen wird.

Synthesis of 1‐(2‐ethyl‐3‐indolyl)‐1‐(3‐pyridyl)ethylene and related ellipticine analogues

AbstractIndole, 2‐methylindole, and 3‐etliylindole have been condensed with acetyl‐ and propionylpyridine, respectively. When propionylpyridine was used as the reactant, the product always was a 1‐(pyridyl)‐1‐indoly[propylene. Condensation of 2‐substituted indoles with 3‐acetylpyridine gave similar products, whereas a similar condensation with 4‐acetylpyridine gave 1,2‐bis(3‐indolyl)‐1‐(4‐pyridyl)ethanes (e.g. 7a). Condensation of unsubstituted indole with 3‐or 4‐acetylpyridine respectively, gave 1,1‐bis(3‐indolyl)‐1‐(pyridyl)ethanes (e.g. 6c).

A REACTION PYRIDOXAL WITH C-3 UNSUBSTITUTED INDOLES.

THE formation of a red pigment from indole and pyridoxal interferes in the enzymatic determination of L-tryptophan1. On the basis of the following evidence, it is proposed that the pigment has the structure IIa shown in Fig. 1 and is therefore analogous to the rosein-doles of Fischer2.