[Chemistry of the cyclic tautomer of tryptophans]

A historical development of the chemistry of cyclic tautomer of tryptophan is reviewed. The cyclic tautomer of tryptophan, pyrrolo [2,3-b]indole-2-carboxylic acid, was prepared by dissolving N-methoxycarbonyltryptophan ester derivatives in 85% phosphoric acid or trifluoroacetic acid. The cyclic tautomer can be reverted to the indolic form with a dilute acid. The cyclic tautomer is an aniline derivative and the enamine reactivity of the indole ring in tryptophan is protected. The electrophilic substitution and oxidation of these cyclic tautomers opened a new method to prepare 5-substituted and/or 6-substituted tryptophan derivatives such as 5-bromo-, 5-hydroxy, and 6-methoxy-tryptophans. The formation and reactions of cyclic tautomers of diketopiperazines containing tryptophan and 3-indoleacetamide are also discussed. Some indole alkaloids having substituents at the benzene ring such as fumitremorgins, flustramine B, and eudistomines were synthesized by the use of these reactions. Furthermore, enantioselective alkylations of the carbanion at the 2-position of the cyclic tautomer established a new route to optically pure alpha-substituted tryptophans. The 2,3-dehydro derivative of the cyclic tautomer is an alpha, beta-unsaturated ester and was found to be a good precursor of optically pure beta-substituted tryptophans. The 3a-position of the cyclic tautomer is a benzylic position and subjected to radical reactions to give 3a-substituted-pyrroloindoles.