Addition Reactions and Wagner-Meerwein Rearrangements in the Indoxyl Series

Witkop, Bernhard; Patrick, James B.

doi:10.1021/ja01146a066

Cited by 78 publications

(23 citation statements)

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“…Within the dehydration step, it is likely that the removal of the non-exchangeable alkyl hydrogen is rate-limiting over the loss of water, causing the step to be isotope-insensitive. A similar reaction involving the reduction of spiro-(cyclopentane-1,2Ј-pseudo-indoxyl) is known to produce a dihydro derivative that is highly analogous to I2 (21). Conversion of this dihydro derivative into tetrahydrocarbazole occurs readily in the presence of trace acid.…”

Section: Solvent Viscosity and Isotope Effects Reveal The Rate-determmentioning

confidence: 99%

Functional Identification of the General Acid and Base in the Dehydration Step of Indole-3-glycerol Phosphate Synthase Catalysis

Zaccardi

Yezdimer

Boehr

2013

Journal of Biological Chemistry

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Background: Bacteria require the enzyme indole-3-glycerol phosphate synthase for the production of Trp. Results: Glu-51 and Lys-53 are identified as the base and acid acting in the dehydration step of enzyme catalysis. Conclusion: Ring closure and dehydration steps are catalyzed by distinct active-site surfaces. Significance: Enzyme inhibitors targeted against these active-site surfaces may serve as novel antibiotics.

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Section: Solvent Viscosity and Isotope Effects Reveal The Rate-determmentioning

confidence: 99%

Functional Identification of the General Acid and Base in the Dehydration Step of Indole-3-glycerol Phosphate Synthase Catalysis

Zaccardi

Yezdimer

Boehr

2013

Journal of Biological Chemistry

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“…Spot C contained an indole trimer and indoxyl red. The indoxyl red, which gave the spot its red color, was probably produced after chromatography by reversal of the reaction that formed the trimer (58). The m/z ratios are the same for 2,2-bis(3Ј-indolyl)indoxyl (the trimer shown in Fig.…”

Section: Resultsmentioning

confidence: 89%

“…They have been generated in vitro by oxidation of indole, using peracetic acid (58), by radiation (29), and by catalysis (10,20). The reactions proceed through a 3-oxo-indole rather than a 3-nitrosoindole intermediate.…”

Section: Discussionmentioning

confidence: 99%

Production of 3-Nitrosoindole Derivatives by Escherichia coli during Anaerobic Growth

Kwon

Weiss

2009

J Bacteriol

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When Escherichia coli K-12 is grown anaerobically in medium containing tryptophan and sodium nitrate, it produces red compounds. The reaction requires functional genes for trytophanase (tnaA), a tryptophan permease (tnaB), and a nitrate reductase (narG), as well as a natural drop in the pH of the culture. Mass spectrometry revealed that the purified chromophores had mass/charge ratios that closely match those for indole red, indoxyl red, and an indole trimer. These compounds are known products of chemical reactions between indole and nitrous acid. They are derived from an initial reaction of 3-nitrosoindole with indole. Apparently, nitrite that is produced from the metabolic reduction of nitrate is converted in the acid medium to nitrous acid, which leads to the nitrosation of the indole that is generated by tryptophanase. An nfi (endonuclease V) mutant and a recA mutant were selectively killed during the period of chromophore production, and a uvrA strain displayed reduced growth. These effects depended on the addition of nitrate to the medium and on tryptophanase activity in the cells. Unexpectedly, the killing of a tnaA ؉ nfi mutant was not accompanied by marked increases in mutation frequencies for several traits tested. The vulnerability of three DNA repair mutants indicates that a nitrosoindole or a derivative of a nitrosoindole produces lethal DNA damage.Under hypoxic conditions, nitrate replaces oxygen as the preferred electron acceptor in Escherichia coli. The nitrate is first reduced to nitrite by periplasmic and cytoplasmic nitrate reductases, and then nitrite is reduced directly to ammonia by nitrite reductases (22). The nitrite, which is an intermediate, is in equilibrium with molecular nitrous acid (HNO 2 ), which can condense with the loss of water to form N 2 O 3 (dinitrogen trioxide, nitrous anhydride). N 2 O 3 is a harmful nitrosating agent that reacts with many cellular constituents, including DNA (57). The N nitrosation of the exocyclic amines of the nucleobases in DNA results in mutagenic deamination (46) and cross-linking of strands (26). Nitrosation of ring nitrogens in DNA destabilizes the glycosylic bond, leading to depurination (36). The nitrosation of secondary amines and amides can turn them into mutagenic alkylating agents (42, 51). The cell is protected from potential damage by high nitrite reductase activity, by a membrane pump that extrudes excessive nitrite, and by the low pK of HNO 2 , which results in an unfavorable equilibrium for its production at neutral pH (22). Nevertheless, nitrosative mutagenesis does occur under these conditions (56). It results mainly from the apparent production of a small amount of nitric oxide as a by-product of cytoplasmic nitrite reductase (12). The nitric oxide is auto-oxidized to N 2 O 3 when the culture is exposed to air (56).For study of nitrosative mutagenesis under hypoxic conditions, E. coli was grown in sealed tubes in a medium containing nitrate as an electron acceptor (56). In this study, we report our observation that some strains forme...

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“…The infra-red spectra of dimers and trimers of indole and 2 methyl indole were recorded by Witkop and Patrick [9]. It appears that bands which are generally attributed to the aromatic ring system retain their pattern upon polymerization, showing only small increases in vibration frequencies and some changes in the relative intensities.…”

Section: Configuration (J)mentioning

confidence: 99%