Indolyl radicals, reactions

A radical ipso substitution at the 3-position of 2,3-disubstituted indoles has also been reported in their reaction with benzoyl-r-butyl nitroxide leading to (227) or, with the 2-substituted indole, the dimer (228) (cf. Section 3.05.1.4) (81CC694). In contrast with the benzoyloxylation reactions the nitroxide radical initially abstracts the hydrogen atom at the 1-position to form the indolyl radical. This mechanism is supported by the failure of the corresponding 1 -methylindole to undergo an analogous oxidation. 

It is necessary that an antioxidant protects cells at all stages of oxidative stress, and therefore an antioxidant should be able to scavenge the secondary radicals produced by the reaction of primary radicals with biomolecules. Radiation chemists designed methods to study reactions of secondary radicals from amino acids of proteins and base and sugar radicals of DNA with antioxidants.The most commonly employed aromatic amino acid radicals generated by radiation chemical experiments are the indolyl radicals of tryptophan (TRP ), the... 

The intramolecular one-electron redox reaction (equation 1) involves electron transfer from the phenol group of the tyrosine side chain to the indolyl radical of the tryptophan side chain (Trp ). 

Photocyclization of iV-chloroacetyl amines has been used previously in the synthesis of nitrogen heterocycles, and the reaction of the substituted amine (166) leads to a benzazepinone that can be elaborated to give pseudoprotopine alkaloids. Y-Chloroacetyl derivatives of the seven isomeric indolylethylamines give azepinoindoles and azocinoindoles by photocyclization. Quantum yields for the reaction are correlated with calculated (CNDO/2 and INDO) electron densities, and on this basis mechanisms are suggested the conclusion is that both indole radical cations and indolyl radicals (for the 1-substituted compounds) are... 

Reaction of indole 109 with a number of alkenes llOa-d is described (99CC1761). The expedient use of a catalytic amount of BusSnCl in the presence of reducing agent NaCNBHs, ensured that the lowest concentration of BuaSnH was obtained (86JA303). Further examples are available in the original report, outlining the reactivity of the 2-indolyl radical towards a number of alkenes. Noteworthy in their approach, is... 

Following their investigation on the reactivity of 2-indolyl radicals, Jones (00TL4209) reported on their intramolecular addition reactions to benzene rings tethered to the nitrogen of the indole with various length chains (Scheme 28). 

The main source of thiyl radicals in cells is expected to be reaction (1), because of the relative abundance of C-H bonds. Some biological radicals are nitrogen-or oxygen-centered, such as the tryptophan (indolyl) radical in DNA photolyase [45], and indolyl and tyrosine (phenoxyl) radicals in ribonucleotide reductase [46-49]. Whether oxygen-centred radicals such as phenoxyl radicals (PhO, e.g. from tyrosine) oxidize GSH by hydrogen transfer ... 

In an alternate mode of radical cyclization, indolyl-2-radicals generated from the corresponding 2-bromo derivatives 152 (n=l-3) undergo intramolecular reactions with appended aromatic rings to afford fused [ 1,2-a]indoles 153 <00TL4209>. 

Examples of reaction mechanisms which involve nucleophilic attack on pyrrolyl and indolyl cations and radical cations are cited elsewhere. 

The UV photochemistry of phenol and related systems (such as indole, pyrrole, imidazole) is dominated by a hydrogen detachment reaction which is driven by repulsive 1ira states [33,35 10], For the isolated chromophores, the 1 mr -driven photodissociation has been explored in unprecedented detail by high-resolution photofragment translational spectroscopy [40], The OH (or NH) bond is broken homolytically, resulting in the formation of two radical species, the hydrogen atom and the phenoxy (or indolyl, etc.) radical. Ion pair formation (abstraction of protons) is energetically not feasible for isolated photoacids. 

Indoles can be used as radical acceptors instead of 63 [120, 121]. Simple and twofold reactions giving either 3-alkylindoles [120] or l,l-bis(3-indolyl)alkanes [121] were observed in 16-72% and 54-90% yield, respectively. In both methods the indole is subject to radical addition in 3-position. The resulting a-amino radical undergoes a further oxidation and deprotonation to the 3-substituted indole. In the case of twofold additions, the second indole unit is introduced by a subsequent polar Friedel-Crafts-type alkylation. 

Indolylacyl radicals undergo intramolecular reactions with benzene <04TL5605>, pyridine <05JOC9077> and quinoline <06OL561> rings with moderate to excellent efficiency, enabling the assembly of polycyclic aryl or heteroaryl indolyl ketones related to natural and synthetic bioactive compounds. 

Indolylacyl radicals are extremely useful reactive intermediates that participate in inter-and intramolecular reactions with alkenes and (hetero)aromatic systems. This radical methodology gives easy access to a wide range of indolic structures, including simple indolyl ketones as well as more complex polycyclic compounds embodying the 2-acylindole moiety. 

Reactions are fast with aromatic residues (k= 10 mol 1 s f). They begin by OH addition to the ring. With phenylalanine, addition occurs preferentially on the ortho position relative to -CH2CHCONH group (55). For tyrosine, addition takes place mostly at the ortho position relative to the phenol function. However, in both cases additions can also be expected on other positions. In tryptophan, the indole ring is more reactive than the phenyl one. OH-adducts may release OH giving phenoxyl (from tyrosine) or indolyl (from tryptophan) radicals whose absorption spectra are well characterized (table 3). 

Some other, apparent cycloadditions probably proceed by non-concerted pathways, for example addition of 1,3-cyclohexadiene in the presence of light and 2,4,6-triphenylpyrylium, probably involves radical intermediates, and reactions of 2-phenylsulfonyl-dienes with indolyl Grignard reagents probably proceed in stepwise fashion as shown. "... 

S. A. Raw (AstraZeneca, UK) and R. J. K. Taylor (University of York, UK) describe novel developments in the preparation and applications of 1,2,4-triazines, especially inverse electron demand Diels-Alder reactions. Heteroaryl radicals, with particular emphasis on pyridyl, indolyl, and thienyl radicals, in which the unpaired electron occupies an sp orbital orthogonal to the Jt-system are covered by D. Mirizzi and K. Jones (Institute of Cancer Research, London, UK) and S. T. Hilton (School of Pharmacy, University of London, UK). 

Amides and imides. The photochemical decarbo>ylation of acryloylojy-substituted long-chain carboxylic acids opens a path to macrocyclic lactams through radical photocyclization. Pyrrolyl and indolyl benzoxazoles have been obtained from the intramolecular O arylation in photostimulated reactions.The photocyclization of the... 

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