Indole quenching

Under acetone sensitization, 3-substituted indoles couple with 5-bro-mo-l,3-dimethyluracil at the indole 2-position (Scheme 29). It is proposed that this reaction proceeds via electron transfer from indole to the uracil triplet excited state since better electron donors than indole quench the reaction [14a, 64,65]. A similar reaction occurs when indole or 3-methylin-dole is photolyzed w ith 3,4-dibromo-AT-methylsuccinimide (Scheme 30) [65]. The quantum yield of this reaction is 0.14 in cyclohexane and 0.49 in diethyl ether, and drops to 0.02 in acetonitrile, which suggests that full electron transfer and radical ion-pair separation does not occur in this case. 

Joule discovered a novel route to [6]-fused indoles via an interesting sequence that involved C2-lithiation of indole, quenching with either lactam [154] or lactone electrophiles [105, 155, 156], and subsequent intramolecular cycUzatiOTi reactions with consequent loss of the benzenesulfonyl group. Their synthesis of oxepino-fused indole 33 is instructive (Scheme 5) [155]. Treatment of 24 with phthalide (31)... 

The in situ generation of the carbon dioxide adduct of an indole provides sufficient protection and activation of an indole for metalation at C-2 with r-butyl-lithium. The lithium reagent can be quenched with an electrophile, and quenching of the reaction with water releases the carbon dioxide. ... 

Preparation of bromoindoles by replacement of metallic substituents have included oxidation of indolylmagnesium bromide by p-nitrobenzoic acid to give 3-bromoindole (67BSF1294), thallation procedures (illustrated in Scheme 18 also applied to the synthesis of chloroindoles) [85H(23)3113 86H(24)3065 87CPB3146, 87H(26)2817 89H(29)1163], and the use of lithium derivatives. The thallation reactions provide access particularly to 4- and 7-bromoindoles. Quenching the protected 2-lithium derivative of indole with 1,2-dibromotetrachloroethane gave an 87% yield of 2-bromoindole (92JOC2495). 

Eftink, M.R. and Chiron, C.A. (1984) Indole fluorescence quenching studies on proteins and model systems use of the efficient quencher succinimide. Biochemistry 23, 3891-3899. 

The study of Fuji et al. shows that the addition of lithium enolate 75 to ni-troamine 74 is readily reversible quenching conditions are thus essential for getting a good yield of product 76. An equilibrium mixture of the adducts exists in the reaction mixture, and the elimination of either the prolinol or lactone moiety can take place depending on the workup condition (Scheme 2-34). A feature of this asymmetric synthesis is the direct one pot formation of the enantiomer with a high ee value. One application of this reaction is the asymmetric synthesis of a key intermediate for indole type Aspidosperma and Hun-teria alkaloids.68 Fuji69 has reviewed the asymmetric creation of quaternary carbon atoms. 

Palmisano and Santagostino first reported Stille reactions of indole-ring stannylindoles with their detailed studies of 1V-SEM stannane 159 [170], Thus 159, which is readily prepared by C-2 lithiation of A-SEM indole and quenching with Bu3SnCl (88%), couples under optimized Pd(0)-catalyzed conditions to give an array of cross-coupled products 160. Some other examples and... 

M. R. Eftink and C. A. Ghiron, Fluorescence quenching of indole and model micelle systems, J. Phys. Chem. 80, 486 193 (1976). 

The phosphorescence lifetimes of various proteins at room temperature are given in Table 3.1. Some variability in the lifetimes reported from lab to lab is evident, possibly due to different enzyme preparation, removal of oxygen (see below), or other conditions. Nevertheless, when measured under the same conditions, it is apparent that the tryptophan lifetimes vary dramatically from protein to protein. Alkaline phosphatase exhibits the longest lifetime from a protein in solution with a lifetime of 1.5—1.7 s at 22°C, approaching the lifetime of 5.5 s at 77 K. The lifetime of free indole in solution is 15—30 /is at 22°C.(38 39) Therefore, in the absence of other quenching mechanisms, the lower limit for the phosphorescence lifetime of a fully exposed tryptophan moiety in a protein should be about 20 /is. 

Neither Fj nor F2 alone gave the characteristic fluorescence of fa and nicked fa in the presence of L-serine and pyridoxal phosphate. However, titration of a fixed amount of F2 with F2 gave rise to a fluorescence intensity 80-90% that of nicked fa at a stoichiometric ratio of Ft to F2. Moreover, both the excitation and emission spectra of the stoichiometric mixture were the same as for nicked fa. In addition, the same specific quenching of this fluorescence was shown in recombined Fj and F2 as in nicked fa. Further, the dissociation constants for L-serine and for indole were determined to be the same within experimental error for recombined Fj and F2, as for nicked fa. No significant differences were found between nicked fa and reconstituted Fj F2 in the intrinsic fluorescence of the aromatic residues, or in the sedimentation coefficients or the 200-250 nm CD spectra. From the foregoing independent lines of evidence, F2 and F2 combine to produce a structure very similar to that of nicked fa. 

Various organolithium intermediates may be posmlated for the synthesis of functionalized indoles and other heterocyclic compounds, from substituted Af-allylanilines (331a-c) or the cychc analog 332, on treatment with f-BuLi. For example, in equation 81 intermediate 333, derived from 331a, was quenched with deuterium oxide. Participation of benzyne metallated intermediates, such as 334, derived from 332, is surmised in equation 82 and other processes. The products of equations 81 and 82 can be characterized by H and NMR spectra . 

Much more versatile than the simple anilines are their anilide derivatives. PivalaniUdes, benzanilides and other non"° (or scarcely ) enolizable amides 549 are laterally lithiated on treatment with two equivalents of BuLi, and may be quenched with electrophiles to give 551. In the absence of an electrophile, the organoUthiums 550 cyclize to indoles 552 (Scheme 218). 

The anisotropy decay of the tryptophan fluorescence of both model peptides and biologically active peptides containing a single tryptophan residue has been determined in various studies. Even in the case of the tripeptide H-Gly-Trp-Gly-OH quenched by acrylamide the anisotropy decay displayed two correlation times with values of 39 and 135 ps. 44 The shorter correlation time was thought to be due to motions of the indole ring relative to the tripeptide. In the case of ACTH(l-24) the fluorescence anisotropy decay of the single tryptophan residue in position 9 of the peptide sequence obtained in phosphate buffer (pH 7, 3.5 °C) was also double-exponential. 29 The shorter rotational correlation time (0 = 92ps)... 

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