Enantiospecific synthesis with amino acids. Part 1. Tryptophan as a chiron for the synthesis of α-substituted tryptophan derivatives

Abstract

N _α -Methoxycarbonyl-(S)-tryptophan methyl ester is cyclised with 85% phosphoric acid to give (2S,3aR,8aS)-1,2-bis(methoxycarbonyl)-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole which on reaction with toluene-p-sulphonyl chloride gives (2S,3aR,8aS)-1,2-bis(methoxycarbonyl)-8-(p-tolylsulphonyl)-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole. This compound undergoes deprotonation with lithium diisopropylamide to the corresponding enolate which is quenched with a variety of alkylating agents resulting in alkylation, with retention of configuration, at C-2 of the pyrroloindole system. Subsequent treatment with trifluoroacetic acid brings about cycloreversion affording essentially optically pure α-alkylated tryptophan derivatives. The process is also applied, in the R-series.