Labelling of the indole nucleus of tryptophan at the 2-position

Tryptophan may be converted in high yields to the 2-hydroxy-derivative by reaction of sulfenyl halides and subsequent hydrolysis in 20% acetic acid at high temperature of the 2-thioaryl-compound. 2-Thiol-tryptophan and related compounds have been obtained by reduction of the tryptophan dimers obtained by reaction with sulfur dicholoride (S2Cl2). Novel methods of isotopic labelling the indole moiety at the 2-position have been also developed. 2-Thioaryl-indole derivatives with a propionic acid side chain at the 3-position are converted by one equivalent of N-bromosuccinimide in bicarbonate solution to lactones, which upon reduction with NaBH4 (or NaBD4 or NaBT4) give indole-propionic acid derivatives (or 2-labelled compounds thereof). The incorporation of deuterium or tritium was approximately 80%.