The dye-sensitized photooxygenation of DLtryptophan in aqueous solution leads to the tricyclic compound 2-carboxy-3a-hydroperoxy-1, 2,3,3a,8,8a-hexahydropyrrolo[2,3-blindole 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 2280) 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-blindole, 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 2280, 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. The first direct chemical conversion of tryptophan (1) to formylkynurenine (4) was by ozonolysis (1). The biochemical degradation of L-tryptophan by L-tryptophan oxygenase, a dioxygenase [L-tryptophan:oxygen 2,3-oxidoreductase (decyclizing), EC 1.13.11.11], served as one of the first demonstrations of the incorporation of both 180 moieties of molecular oxygen (1802) (2) and prompted many model studies involving intermediary hydroperoxides arising from indole substrates through. catalytic oxidation (3) or photooxygenation (4, 5).(See structure cut on top of next page.) Earlier studies (6-13; for reviews, see refs. 14 and 15) on the sensitized photooxygenation of 1 led to complicated mixtures of products in which kynurenine was detected (7) and formylkynurenine was isolated in low yield (12). In accord with the general mechanism of oxidations of enamines (16) 3-hydroperoxyindolenine (4, 21-24). Furthermore, we have found a new reaction pathway to kynurenine via the long-sought-after 3a-hydroperoxyhexahydropyrroloindole (23, 24).The reinvestigation of the dye-sensitized photooxygenation of tryptophan itself in aqueous solution has now led to the major product, 3a-hydroperoxypyrrolidinoindole (7) which easily rearranges to formylkynurenine (4) upon warming.
EXPERIMENTALWhen an aqueous solution (300 ml) of DL-tryptophan (1) (1 g, 5 mmol) containing EtOH (15 ml) and Rose Bengal (0.4 mmol) was photooxygenated at 0°-5°for 2.5 hr, followed by reduction with dimethyl sulfide, the 3a-hydroxyhexahydropyrroloindole (8) was obtained as a mixture of two diastereoisomers that were readily separated by fractional crystallization from water to give 8a, mp 254°-256°(28%) and 8b, mp 2280 (28%), in addition to 23% of recovered tryptophan (1). The spectral properties of 8 were in complete accord with those reported by Savige (25) who obtained 8 by oxidation of 1 with peracetic acid. Neither formylkynurenine no...
