Synthesis of three isotopomers of L‐tryptophan via a combination of organic synthesis and biotechnology

Abstract

Abstract In this paper, we report the preparation of three isotopomers of L‐tryptophan on a gram scale, specifically labelled with 99% 15 N (position 1) and 99% 13 C (position 2) in the indole ring; for position 3, the incorporation was 90% 13 C. The isotopically enriched indoles were synthesized from H 15 NO 3 , K 13 CN and 13 CH 3 CN and then converted, with L‐serine, into the correspondingly labelled L‐tryptophans using genetic manipulated E. coli bacteria, which contain high amounts of the enzyme tryptophan synthetase. The 13 C‐ 13 C, 13 C‐ 1 H, 13 C‐ 15 N and 15 N‐ 1 H coupling constants of the indoles and the tryptophans were determined from the 1 H NMR and 13 C NMR spectra.