Wakamatsu K, Ito S
School of Hygiene, Fujita-Gakuen Health University, Aichi, Japan.
Anal Biochem. 1988 May 1;170(2):335-40. doi: 10.1016/0003-2697(88)90639-2.
5,6-Dihydroxyindole (5,6DHI) and 5,6-dihydroxyindole-2-carboxylic acid (5,6DHI2C) are ultimate precursors of the black melanin, eumelanin. These indolic metabolites and their O-methyl derivatives are excreted in urine of melanoma patients at high levels and of healthy persons at low levels. We describe here a simplified procedure for preparing milligram to subgram quantities of 5,6DHI and 5,6DHI2C and their O-methyl derivatives. Dopachrome generated in situ by ferricyanide oxidation of dopa at pH 6.5 underwent spontaneous decarboxylation to give 5,6DHI in 40% isolation yield, while treatment of dopachrome with alkali at pH 13 afforded 5,6DHI2C in 38% isolation yield. Two isomeric O-methyl derivatives of 5,6DHI were prepared by treatment with diazomethane, while those of 5,6DHI2C were prepared by treatment with diazomethane followed by alkaline hydrolysis of the methyl esters. 5,6DHI and 6-hydroxy-5-methoxyindole were also obtained by heating the corresponding carboxylic acids in decalin. 5-Hydroxy-6-methoxyindole and 6-hydroxy-5-methoxyindole-2-carboxylic acid could also be prepared by debenzylation of the commercially available O-benzyl derivatives.
5,6 - 二羟基吲哚（5,6DHI）和5,6 - 二羟基吲哚 - 2 - 羧酸（5,6DHI2C）是黑色真黑素的最终前体。这些吲哚类代谢产物及其O - 甲基衍生物在黑色素瘤患者尿液中高水平排泄，而在健康人尿液中低水平排泄。我们在此描述一种制备毫克至亚克量的5,6DHI、5,6DHI2C及其O - 甲基衍生物的简化方法。在pH 6.5下，通过铁氰化物氧化多巴原位生成的多巴色素进行自发脱羧反应，以40%的分离产率得到5,6DHI，而在pH 13下用碱处理多巴色素以38%的分离产率得到5,6DHI2C。通过用重氮甲烷处理制备了5,6DHI的两种异构体O - 甲基衍生物，而5,6DHI2C的异构体O - 甲基衍生物则通过用重氮甲烷处理，然后对甲酯进行碱性水解来制备。5,6DHI和6 - 羟基 - 5 - 甲氧基吲哚也通过在萘烷中加热相应的羧酸获得。5 - 羟基 - 6 - 甲氧基吲哚和6 - 羟基 - 5 - 甲氧基吲哚 - 2 - 羧酸也可以通过将市售的O - 苄基衍生物脱苄基来制备。
