Dopachrome rearrangement

Palumbo A, d Ischia M, Misuraca G, De Martino L, Prota G (1994) A New Dopachrome Rearranging Enzyme from the Ejected Ink of the Cuttlefish Sepia officinalis. Biochem J 299 839... 

In 1927 Raper showed that the red pigment obtained on oxidation of DOPA [i.e. 2,3-dihydroindole-5,6-quinone-2-carboxylic acid, dopachrome (4)] rearranged spontaneously by an autoreduction process in vacuo to 5,6-dihydroxyindole (29).72 The rearrangement process could be accelerated by the action of alkali or sulfur dioxide.72 In the latter case, decarboxylation did not accompany the rearrangement and the colorless derivative was 5,6-dihydroxyindole-2-carboxylic acid (17).72 Compounds 17 and 29 were isolated as their dimethyl ethers, (30A) and (30B).72 Immediate decolorization of epinochrome (27) solutions on addition of alkali was reported a few years later.134... 

Subsequent investigations have shown that Raper s suggestion that dopachrome (4) and related aminochromes decompose by an internal oxidation-reduction process forming 5,6-dihydroxyindoles was essentially correct.73,118,120,184-137 The 5,6-dihydroxyindoles obtained from aminochromes such as dopachrome (4) and epino-chrome (27) (i.e. with no substitution in the 3-position) show only a relatively weak blue to blue-mauve fluorescence.118,120 The intense yellow-green fluorescence shown by the rearrangement products of aminochromes with a 3-hydroxyl group is due to the formation of... 

Some reports associate the rearrangement of dopachrome to DI in melanoma with an enzyme distal from tyrosinase (179-182) characterized as an oxidoreductase (183). Owing to the preliminary nature of the supporting experiments, however, the regulatory effect may be associated with the catalytic effect of metal ions rather than that of the new enzyme (184). 

An investigation of the oxidation of melanin precursors in the presence of azide radicals using pulse radiolysis has been reported (2J9. Thus, dopa and cysteinyldopa yielded first the unstable semiquinones that disproportionated to a quinone-quinol complex. The quinones decayed to more stable products dopaquinone produced dopachrome while cystei-nyldopa-quinones rearranged to benzothiazine isomers. 

At pH 7.4 metal ions promote the non-decarboxylative pathway to the acid 2, most likely by enhancing the acidity of the H-2 proton (87BBA203). Notably, however, at pH 5.5, aluminium ions promote the rapid decarboxylative rearrangement of dopachrome leading to 5,6-dihydroxyindole 1 rather than the acid 2 (03MI1689). 

Addition of 5,6-dihydroxyindole 1 to dopachrome may occur during rearrangement and leads to a product that has been identified after reduction and acetylation as compond 148 (87G627). 

In the Raper-Mason scheme of melanin biosynthesis (Fig. 5) 216, 217), tyrosine is enzymatically converted via dopa to dopaquinone. The subsequent oxidation steps leading to melanin formation depend upon the biochemical environment of the reaction site. However, the melanization process in vitro or in vivo has two important features the rearrangement of dopachrome and the oxidative polymerization of 5,6-dihydroxyindoles leading to melanochrome. 

For the rearrangement of dopachrome, one possible mechanism which has been accepted by different authors 66, 218, 255), involves a hydrogen shift from position 3 and the formation of a quinone methide followed by subsequent decarboxylation to 13. Analysis of the anal5hical data from various laboratories 66, 108, 202) has shown that the yield of DHI vs DHICA is about 95 to 5, at a pH range from 3 to 8.5 which indicates that tyrosinase-catalyzed synthetic dopamelanin is made up mainly of DHI-derived units, as proposed by Mason 163). Hence, the... 

The presence of certain metal ions, especially Cu, Fe, Zn etc., in melanin biosynthesis, however, accelerates the non-decarboxylating rearrangement of dopachrome leading to the formation of DHICA rather than DHI (50, 190). 

Further, recent studies 132) have revealed the presence in melanocytes of a melanosomal protein different from tyrosinase, which has the ability to catalyze the rearrangement of dopachrome to DHICA. This enzymic reaction is highly stereospecific for normal L-dopachrome, is unaffected by metal chelators and has an optimal pH of about 6.8. Different names have been proposed for this enzyme, i.e. dopachrome conversion factor 132, 256), dopachrome oxidoreductase 143), dopachrome isomerase 201), and dopachrome tautomerase 4). It is of interest that another enzyme named dopaquinoneimine conversion factor seems to exist which has the remarkable ability to catalyze the decaibox-ylative rearrangement of dopachrome to DHI rather than DHICA 193). 

The oxidation of DHICA was also studied in the absence and presence of DHI, and two dimers (191) and one mixed dimer (180) were identified. The overall results obtained in the oxidation of DHI or DHICA at the melanochrome stage support the concept of eumelanin as an intimate mixture of homopolymers of DHI and DHICA, and copolymers of the two indole units in different proportions, the latter depending upon the ratio of formation of DHI and DHICA in the rearrangement of dopachrome. 

Costantini C, Crescenzi O, Prota G (1991) Mechanism of the Rearrangement of Dopachrome to 5,6-Dihydroxyindole. Tetrahedron Lett 31 3849... 

Dopachrome conversion factor catalyzes the decolorization of dopachrome. The mechanism of this conversion apparently involves an isomeric rearrangement of a hydrogen atom from one position of the dopachrome molecule to another, an intramolecular oxidoreduction which results in a tautomeric shift forming 5,6-dihydroxyindole-2-... 

On irradiation with ultraviolet light, tyrosine is readily converted to DOPA, which is then oxidised further, probably to dopachrome and then to melanin [29, 85-88]. Synephrine (41) behaves similarly, being oxidised first to adrenaline and then probably to adrenochrome which rearranges to adrenolutin [89]. These oxidations probably involved the initial formation of the semi-quinone followed by oxidation to the open-chain quinone [90]. Ultraviolet irradiation was also found to increase the rate of oxidation of tyrosine by tyrosinase in rat skin. OrrAo-quinones were produced in the reaction and it was concluded that the acceleration was due to the formation of low levels of these compounds from tyrosine [91]. 

In acid solution dopachrome (68) rearranges to give mainly 2-carboxy-5,6 -dihydroxyindole (72), while in the pH range 5.6-8.0 the corresponding decarboxylated indole (73) predominates. The mechanism of the metal salt... 

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