Indole-3-acetic acid, oxidation

Scheme 4.15 Fisher indole and oxidation approach to indole acetic acid 2.

The ability of HRP to degrade the plant hormone indole-3-acetic acid (lAA) in the absence of hydrogen peroxide was noted as early as 1955 (136). Plant peroxidases are now known to be of major importance in the metabolism of lAA (137) (note that they are often referred to as indole acetic acid oxidases in the older literature). The mechanism of lAA oxidation by HRP C is complex and has been studied experimentally in great detail by several groups (23, 137). Reaction products include indole-3-methanol, indole-3-aldehyde, and 3-methylene oxin-dole, which is probably a nonenzymatic conversion product of indole-3-methylhydroperoxide. The most important developments in this area have been reviewed (23). 

Most tryptamine molecules are metabolized by the enzyme monoamine oxidase (MAO). MAO actually occurs in two different forms, MAO-A and MAO-B, which have preferences for different neurotransmitter molecules. MAO-A oxidizes the terminal amine of the tryptamines to an imine. This imine then undergoes nonenzymatic hydrolysis to an aldehyde that is subsequently converted to a carboxylic acid by a second enzyme, aldehyde dehydrogenase. The result is the conversion of the tryptamine into an acidic molecule, called an indole-3-acetic acid, which lacks psychoactivity. DMT is converted into indole acetic acid, whereas serotonin is converted into 5-hydroxyindole acetic acid (5-HIAA), and psilocin is converted into 4-hydroxy indole acetic acid. 

From the cinnamic acids or phenyl propanoids described above, / -oxidation and truncation of side chains yields a variety of benzoic or simple phenolic acids [28], Rao et al., [22] identified gallic acid (18), gentisic acid (19), protocatechuic acid (20), />-hydroxybenzoic acid (21), oc-resorcyclic acid (22), vanillic acid (23) and salicylic acid (24) in C. arietinum and showed that overall, leaf content of all phenolic compounds was much greater than in roots and stem. They postulated that the production of these compounds may enhance the activity of indole acetic acid oxidase or may express antimicrobial properties when leached into the soil. However, Singh et al. [24] showed that the production of both 18 and 24 by C. arietinum was induced when treated by the culture filtrate of Sclerotium rolfsii along with the phenyl propanoids 14, 15 and 17 mentioned above. 

Chromium trioxide I acetic acid Oxidative indole ring opening... 

Oxidation with chromium trioxide in acetic acid cleaved the indole ring to produce intermediate 23 which cyclodehydrated to give prazepam (24). 

Snyder and coworkers followed a completely different path to canthin-6-one (Fig. 23). Earlier they had shown that indole-substituted 1,24-triazine 66 could be heated in refluxing triisopropylbenzene (bp = 232 °C) to give /3-carboline 67 via an intramolecular cycloaddition/cycloreversion reaction [58]. Selective oxidation of 67 at C-6 was achieved through the use of triethylbenzylammonium permanganate [59]. Success of the reaction proved to be very sensitive to the solvent chosen. Heating 67 for 4 h at 70 °C in a 5 1 mixture of dichloromethane and acetic acid gave a 65% yield of 63, yet use of increasing amounts of dichloromethane slowed the reaction down (no reaction occurred in pure dichloromethane), while use of pure acetic acid led to an intractable mixture. 

Most of the early applications of palladium to indole chemistry involved oxidative coupling or cyclization using stoichiometric Pd(II). Akermark first reported the efficient oxidative coupling of diphenyl amines to carbazoles 37 with Pd(OAc)2 in refluxing acetic acid [45]. The reaction is applicable to several ring-substituted carbazoles (Br, Cl, OMe, Me, NO2), and 20 years later Akermark and colleagues made this reaction catalytic in the conversion of arylaminoquinones 38 to carbazole-l,4-quinones 39 [46]. This oxidative cyclization is particularly useful for the synthesis of benzocarbazole-6,11-quinones (e.g., 40). 

Indium-tin-oxide anode, 22 215, 216 Indium trichloride, 14 197, 201 Indo-3-lyl acetic acid, 13 284 Indole-3-acetic acid, 13 35, 38. See also Indoleacetic acids (IAAs) Indole-3-butyric acid, 13 25t... 

The double bond in indole and its homologs and derivatives is reduced easily and selectively by catalytic hydrogenation over platinum oxide in ethanol and fluoroboric acid [456], by sodium borohydride [457], by sodium cyanoborohydride [457], by borane [458,459], by sodium in ammonia [460], by lithium [461] and by zinc [462]. Reduction with sodium borohydride in acetic acid can result in alkylation on nitrogen giving JV-ethylindoline [457]. 

Electrochemical oxidation of indole [202] and N-methylindole [203] in acetonitrile gives rise to dimers and trimers. These are oxidised further to polymers. Oxidation of N-acetylindoles in acetic acid results in acetoxylation of the heterocyclic... 

Other orchid metabolites suchs as batatasin 1, inhibited the growth of liverworts, algae and oat coleoptiles. Batatasin 1 also inhibited the CO2 dependent O2 evolution and the flow of electrons from water to methylvi-ologen in spinach chloroplasts, and it inhibited the succinate-dependent O2 uptake in potato tuber mitochondria. Other phenanthrenes such as orchinol, which has a free hydroxyl at the 7-position, inhibit indole-3-acetic acid (lAA) oxidation catalyzed by horseradish peroxidase. 

Beccalli et al. reported a total synthesis of furostifoline (224) starting from indole-3-acetic acid (680) (691). The key step of this strategy is the oxidative... 

These compounds are less common than indole (benzo[ ]pyrrole). In the case of benzo[i>]furan the aromaticity of the heterocycle is weaker than in indole, and this ring is easily cleaved by reduction or oxidation. Electrophilic reagents tend to react with benzo[Z ]furan at C-2 in preference to C-3 (Scheme 7.21), reflecting the reduced ability of the heteroatom to stabilize the intermediate for 3-substitution. Attack in the heterocycle is often accompanied by substitution in the benzenoid ring. Nitration with nitric acid in acetic acid gives mainly 2-nitrobenzo[Z ]furan, plus the 4-, 6- and 7-isomers. When the reagent is in benzene maintained at 10 °C, both 3- and 2-nitro[ ]furans are formed in the ratio 4 1. Under Vilsmeier reaction conditions (see Section 6.1.2), benzo[Z ]furan gives 2-formylbenzo[6]furan in ca. 40% yield. 

Formation of 2-AAP could be traced back to the plant hormone indole-3-acetic acid (lAA) [80], which is formed in the grape berry. The oxidative degra-... 

Triple bonds are in general more reactive than double bonds as is exemplified in the following process (1.2.).13 The active catalyst is HPdOAc, which is formed by the oxidative addition of acetic acid onto Pd(0). The organic substrate is attached to the palladium in a regio- and stereospecific step that is followed by an oxidative addition (N.B. Pd(II)-Pd(IV) transition) and reductive elimination, or alternatively carbopalladation and reductive elimination, to give the indole derivative. 

The synthesis of a C-labelled version of naratriptan (3b) is highlighted in Scheme The indole ring of naratriptan hydrochloride (3) was oxidatively cleaved using sodium periodate to give ketoformanilide 45. Cyanation of 45 with potassium [ C]cyanide in aqueous ethanol gave the intermediate amidine 46, which was reduced directly with NaBH4 in acetic acid to afford C-labelled naratriptan (3b), which was isolated as the hydrochloride salt. 

Halogenomethylpyrroles have been oxidized with lead(IV) salts or by chromium trioxide to yield the formylpyrroles, whilst catalytic hydrogenolysis or zinc-acetic acid reduction produces the 2-methylpyrroles (B-77MI30504). The methyl derivatives are also obtained by hydride reduction of trifluoromethyl-pyrroles and -indoles, and trifluoromethylindoles are converted into the carboxylic esters by ethanol under basic conditions (74JOC1836). 

In contrast with the relatively facile nucleophilic substitution reactions at the 2-position of the indole system, only 3-iodoindole has been reported to react with silver acetate in acetic acid to yield 3-acetoxyindole (59JOC117). This reaction is of added interest as 3-iodo-2-methylindole fails to react with moist silver oxide (72HC(25-2)127). It is also noteworthy that the activated halogen of ethyl 3-bromo-4-ethyl-2-formylpyrrole-5-carboxylate is not displaced during the silver oxide oxidation of the formyl group to the carboxylic acid (57AC(R)167>. 

Indole-3-acetic acid is rather readily oxidized by peroxidases and is, in fact, probably not present in the plant in the free form to any appreciable extent. The nature of the complexing groups is not clear. The inherent instability of the compound in living tissue has made experimental observations difficult, and (the more stable) 1-naphthaleneacetic acid has often been used instead, although it is by no means certain that the biological activities are comparable. One view held is that auxin herbicides are effective either because they do not readily form conjugate systems, or because the conjugate retains the phytotoxic properties. 

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