A valid model for the mechanism of oxidation of tryptophan to formylkynurenine—25 years later

Abstract

The dye-sensitized photooxygenation of DL-tryptophan in aqueous solution leads to the tricyclic compound 2-carboxy-3a-hydroperoxy-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole which, on reduction with dimethyl sulfide, furnishes two diastereoisomeric alcohols separable by fractional crystallization into a higher melting (mp 254°-256°) and a lower melting (mp 228°) diastereoisomer. Each of these alcohols was correlated with one of the analogous pair of isomeric 1,2-dicarbomethoxy analogs by alkaline hydrolysis and by x-ray analysis. In this way, the 3a-hydroxy-1,2-dimethoxycarbonyl- 1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole, mp 163°-164°, was shown to have the trans configuration with regard to the relative positions of the hydroxyl and carbomethoxy groups and that, on alkaline hydrolysis, it produced the isomer with mp 228°, which therefore also has the trans configuration. The mechanism of the smooth thermal rearrangement of the (presumably ring-chain tautomeric) tryptophan hydroperoxy intermediates to formylkynurenine is discussed with its implications for the biological oxidation by tryptophan 2,3-dioxygenase.