Adrenochrome derivatives

The sodium bisulfite addition compounds must have a free (or potentially free) ketone-type carbonyl group, since they readily form derivatives with typical ketone reagents such as semicarbazide and 2,4-dinitrophenylhydrazine.174 Decomposition of these derivatives with alkali gives the corresponding adrenochrome derivatives e.g., adrenochrome monosemicarbazone would be obtained from the semicarbazone of the adrenochrome-sodium bisulfite complex.174 If one accepts Tse and Oesterling s formulation of the adrenochrome-sodium bisulfite complex, the semicarbazone would probably have a basically similar structure (i.e. 82). This type of structure is more... 

Various hydroxyl and amino derivatives of aromatic compounds are oxidized by peroxidases in the presence of hydrogen peroxide, yielding neutral or cation free radicals. Thus the phenacetin metabolites p-phenetidine (4-ethoxyaniline) and acetaminophen (TV-acetyl-p-aminophenol) were oxidized by LPO or HRP into the 4-ethoxyaniline cation radical and neutral V-acetyl-4-aminophenoxyl radical, respectively [198,199]. In both cases free radicals were detected by using fast-flow ESR spectroscopy. Catechols, Dopa methyl ester (dihydrox-yphenylalanine methyl ester), and 6-hydroxy-Dopa (trihydroxyphenylalanine) were oxidized by LPO mainly to o-semiquinone free radicals [200]. Another catechol derivative adrenaline (epinephrine) was oxidized into adrenochrome in the reaction catalyzed by HRP [201], This reaction can proceed in the absence of hydrogen peroxide and accompanied by oxygen consumption. It was proposed that the oxidation of adrenaline was mediated by superoxide. HRP and LPO catalyzed the oxidation of Trolox C (an analog of a-tocopherol) into phenoxyl radical [202]. The formation of phenoxyl radicals was monitored by ESR spectroscopy, and the rate constants for the reaction of Compounds II with Trolox C were determined (Table 22.1). 

The characteristic transient yellow-green fluorescence exhibited by adrenaline solutions that were undergoing oxidation in the presence of alkali was first reported in 1918.182 This phenomenon was later shown to be general, and similar (but usually weaker) fluorescences were observed when other catecholamines were oxidized in alkaline solution.133 Many years were to elapse before the correct explanation of this phenomenon was forthcoming, i.e. that the fluorescent product derived from adrenaline was a rearrangement product of adrenochrome (the red oxidation product of adrenaline). 

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-... 

Isopropylideneascorbic acid (62) has recently been shown to reduce adrenochrome in a similar manner to ascorbic acid the main products are 28 and an isopropylidene derivative of 60, i.e. 63.1 0... 

The syntheses of the monoxime [mono- or di-hydrate, m.p. 178° (decomp.)] and monosemicarbazone [m.p. 223° (decomp.)] of DL-adrenochrome have recently been described by Remizov.191 The majority of previous publications referring to these compounds have dealt with derivatives of adrenochrome prepared initially from L-adrenaline. The picrates obtained from the DL-oxime and dl-semicarbazone of adrenochrome were described as yellow powders, decomposing at 124 and 150°, respectively.191 Remizov also described the formation of highly colored complexes from the interaction of the DL-oxime and DL-semicarbazone with certain metal ions (e.g. Co++, Ni++, Cr+++ Fe++ and Fe+++).191... 

Addition products have been obtained from aminochrome derivatives such as the semicarbazone, with sodium bisulfite. Recently Correia Alves reported the preparation of a compound described as adrenochrome semicarbazone sodium sulfonate (m.p. >300°) by treating a solution of adrenochrome monosemicarbazone (90) in sodium carbonate solution with sulfur dioxide at 40° for several days192 this compound was apparently different from the substance (m.p. 227-228°) obtained in a somewhat similar manner by Iwao193-194 and may be comparable to the compound (83) (m.p. > 300°) previously described in a Belgian patent179 (see Section IV,F). Iwao established the structure of his compound as the sodium salt of epinochrome-3-sulfonic acid monosemicarbazone (93).193... 

In recent months a relatively large number of new aminochrome hydrazone derivatives have been reported. Yamanishi et al. have reported the synthesis of twenty-one adrenochrome hydrazone derivatives (cf. 119) where R = oxalyl, oxamyl, malonyl, succinyl,... 

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. 

A number of psychotomimetic substances—including adrenochrome and adrenolutin which are derived from adrenaline —are indole compounds and are therefore structurally related to 5-hydroxytryptamine. The most extensively studied member of the group—LSD25—is, however, less closely related to 5-hydroxytryptamine than are compounds such as bufotenine. 

Adrenahne and its cyclic derivatives (adrenochrome and adrenolutin) may be oxidised by S-... 

Adrenochrome is produced from adrenaline, noradrenochrome from noradrenaline, and products similar to quinone, which have not yet been clearly defined, derive from serotonin and bufotenin. Cytochromoxidase and ceruloplasmine are the catalysing enzymes. So far... 

The dioximato-manganese(II) catalyst (3) increases the auto-oxidation rate of epinephrine (a catecholamine derivative) in Na2C03-NaHC03 buffer at room temperature. The proposed mechanism presumes the binding of O2 to the Mn complex, followed by the formation of a ternary intermediate active catalyst-02-substrate complex which disproportionates in the rate-determining step to the product adrenochrome. ... 

The name adrenochrome was proposed in 1937 by Green and Richter for the unstable red crystalline product obtained on enzymatic oxidation of adrenaline [22], In the same year Richter and Blashko obtained a crystalline iodo-derivative of adrenochrome by the oxidation of adrenaline with potassium iodate [23]. Thus the product responsible for the violet chromogen utilised in one of the original adrenaline assay procedures [10], was only isolated and characterised 30 years after the procklure was first described. 

R = I). However spectra suitable for comparison purposes have been obtained from 7-iodoadrenochrome methyl ether (67, R = Me R = H R = OMe R = I) and adrenochrome methyl ether (67, R = Me R = H R = OMe R = H). The solutions of the 7-iodo derivative mentioned above, were, however somewhat unstable and there was some evidence that a slow deiodination reaction occurred [144]. 

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