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

In this paper, we report the preparation of three isotopomers of L‐tryptophan on a gram scale, specifically labelled with 99% 15N (position 1) and 99% 13C (position 2) in the indole ring; for position 3, the incorporation was 90% 13C. The isotopically enriched indoles were synthesized from H15NO3, K13CN and 13CH3CN 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 13C‐13C, 13C‐1H, 13C‐15N and 15N‐1H coupling constants of the indoles and the tryptophans were determined from the 1H NMR and 13C NMR spectra.