Indole derivatives 5,6-dihydroxy

The alkali metal borohydrides reduce aminochromes in solution very rapidly 70,109,120,147,148,1B1,1B5,157 the expected 5,6-dihydroxy-indole derivative was usually obtained in high yield.161,166 Reduction of the 7-iodoaminochromes was not usually accompanied by deio-dination to any appreciable extent.109,166 A number of relatively minor, unidentified, often fluorescent, water-soluble by-products were usually also detected in the reduction mixtures.109,148,155... 

The 3-alkoxyaminochromes rearrange to form non-fluorescent compounds, probably 3-alkoxy-5,6-dihydroxyindoles [160] (e.g. adrenochrome methyl ether (51) would be expected to rearrange to 5,6-dihydroxy-3-methoxy-Af-methylindole (70)). However, these indole derivatives appear to be readily oxidis in air and have not yet been isolated in pure form. 

The reduction of adrenochrome (1) with ascorbic acid (59) was first reported in 1948,158 although the nature of the reaction products (which may be of physiological importance, cf. ref. 159) was not determined until several years later. It was shown by Heacock and Laidlaw in 1958 that reduction mixtures of this type contained at least three indolic products,147 one of which was isolated and shown to be 5,6-dihydroxy- -methylindole (28).147 The major component of aqueous adrenochrome-ascorbic acid reaction mixtures has recently been shown to be a secondary product (60) (which was isolated as its di- and tetra-acetyl derivatives) produced by the interaction of the o-dihydroxy group of 28 with the a-dicarbonyl function of dehydro-... 

The n.m.r. spectra of several 5,6-dihydroxyindoles (and their diacetyl derivatives) obtained by reduction of different non-halo-genated aminochromes were compared with those obtained from the appropriate 5,6-dihydroxy-(or 5,6-diacetoxy)-iodoindoles produced by reduction of the corresponding iodoaminochromes. The n.m.r. data clearly demonstrated the presence of a- and /3-protons in the indole nuclei (except in the case of the products derived from 2-methylnoradrenochrome and the corresponding iodoaminochrome,... 

Dihydroxy-N-methylindole 142 readily reacts with DHA in aqueous solution at room temperature (64CJC1401 65JCS4728) (Scheme 34). The two hydroxy groups of the indole interact with the a-diketone function of DHA to form the 1,4-benzodioxane 144. This type of reaction appears to be general since similar interactions occur between other o-diphenols and a-diketones. The mechanism by which the 1,4-benzodioxane derivative is obtained when adrenochrome 141 is reduced with ascorbic acid to give 142 via 143 was studied. 

Aromatic substances are oxidized to hydroxyderivatives and dihydroxy-derivatives. Benzene (1) is converted through an instable epoxidic form (2) to phenol (3) which is further oxidized to form pyrocatechol (4) or hydro-quinone (5). The muconic acid (6) is the terminal oxidation degree, being formed by opening the benzene ring. In this way, not only monocyclic but also polycyclic hydrocarbons are oxidized, such as quinoline, indol and coumarins. Some substances are even oxidized to water and carbon dioxide... 

Harley-Mason, J, Melanin and Its Precursors. Part VL Further Syntheses of 5 6-Dihydroxy indole and its Derivatives ... 

Melanin, the black and brown hair and skin pigment in humans and animals, also contains indole units, in particular 5,6-dihydroxyindole. It is derived from the amino acid tyrosine via DOPA (3,4-dihydroxy-phenylalanine) ... 

The structure of the 5,6-dihydroxyindole thioether was finally established by a study of the adrenochrome-thioglycollic acid reaction products. This reaction gave three major indolic products the reduction product 5,6-dihydroxy-A -methylindole (44) the thioether (120) or (121) and a small amount of a third unidentified product [238]. It was not possible to isolate the thioether directly but a stable crystalline acetyl derivative was obtained [242]. The structure of this product was established mainly on the basis of n.m.r. spectroscopic evidence. It was shown that, in fact, the thiol residue was attached to the 4-position (i.e. 4-5 -carboxymethylthio-5,6-dihydroxy-7V-methylindole, (123)) in the indole ring system, since the characteristic long-range coupling of ca. 0-8 Hz which occurs between the protons in the... 

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