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.