R. Marchelli, O. Hutzinger, R. Heacock
Dec 1, 1969
Citations
0
Influential Citations
7
Citations
Journal
Canadian Journal of Chemistry
Abstract
A procedure for the synthesis of the 4-, 5-, 6-, and 7-hydroxyindole-3-carboxylic acids starting from the corresponding 4-, 5-, 6-, and 7-benzyloxyindoles respectively has been devised. The benzyloxyindoles are converted to mixtures of their 1- and 3-carbethoxy derivatives by the action of ethyl chloroformate on their Grignard reagents. The hydroxyindole-3-carboxylic acids are then obtained by the alkaline hydrolysis and debenzylation of the benzyloxy-3-carbethoxyindoles. Canadian Jouinal of Chemistry, 47,4375 (1969) In view of their importance in biology and medicine [cf. review by Cerletti (I)], the metabolism of indole compounds in plants and animals has been the subject of extensive studies in the past. In recent years the importance of the hydroxyindoles (cf. 2, 3), has also been recognized. Whilst a considerable amount of research has been carried out on the metabolism of 3-indolylacetic acid (cf. 4, 5), very little has been reported on the metabolism of indole-3-carboxylic acid. Acheson and King reported that the urine of rats which had been fed or injected intraperitoneally with indole-3-carboxylic acid, contained the original acid (ca. 2073, the corresponding glucuronide, and 6-hydroxyindole-3-carboxylic acid (6). These authors further reported that oxidation of indole-3-carboxylic acid with a model hydroxylating system (Fez', ascorbic acid, EDTA, oxygen) (cf. 7, 8) gave 5- and 6-hydroxyindole-3-carboxylic acid, indole, anthranilic acid, N-formylanthranilic acid, and a number of unidentified products. In other instances the oxidation of indole compounds with this system [i.e. indole (9), tryptophan (9) and skatole (lo)], has resulted in the formation of all 4 hydroxyindole derivatives, hydroxylated in the benzene moiety of the indole ring, together with other products produced by oxidation of the pyrrole ring. Before reinvestigating the hydroxylation of indole-3-carboxylic acid, it was desirable to have available authentic samples of the 4-, 5-, 6-, and 7-hydroxyindole-3-carboxylic acids. The synthesis of these 4co1npounds is described in this paper. R, Values have been reported for both 5- and 6-hydroxyindole-3-carboxylic acids (6, 1 1, 12),