Indolyl carboxylic acids by condensation of indoles with alpha-keto acids

The novel indole derivatives 2,2-bis(3,3'-indolyl)propionic acid (1); 1,1,1,-tris(3,3',3"-indolyl)ethane (2); and 2,2-bis(3, 3'-indolyl)isocaproic acid (3) were isolated from solvent extracts of indole-supplemented supernatants of Escherichia coli and corynebacteria. The compounds were also obtained by chemical synthesis: compounds 1 and 2 from indole and pyruvic acid and compound 3 from indole and alpha-ketoisocaproic acid, following incubation at 37 degrees C in aqueous medium. Tryptophan and pyruvic acid gave the novel 2-(2-tryptophanyl)lactic acid (4). The condensation reaction between indoles and alpha-keto acids was of general nature, and the mild reaction conditions suggested it may proceed in vivo. Examples for endogenous occurrence may be the neuro-degenerative diseases phenylketonuria and maple syrup urine disease, both characterized by elevated blood levels of alpha-keto acids.