Chemo‐enzymatic synthesis and characterization of L‐tryptophans selectively 13C‐enriched or hydroxylated in the six‐membered ring using transformed Escherichia coli cells

Abstract L‐(3a‐ 13 C)‐ And L‐(6‐ 13 C)tryptophan have been synthesized from simple labelled compounds via a single reaction scheme based on the conversion of 1,3‐cyclohexanedione into indole. The labelled indoles have been converted in one step into the corresponding L‐tryptophans using transformed Escherichia coli cells with large amounts of the enzyme, tryptophan synthetase. The same reaction scheme has been used for the synthesis of 4‐ and 7‐indolol. These hydroxyindoles together with 5‐indolol have been converted into 4‐, 7‐ and 5‐hydroxy‐L‐tryptophan, respectively, using the Escherichia coli cells. The latter compound is the immediate precursor of the neurotransmitter, serotonin. It appears that 7‐indolol is the only indole derivative which is converted faster than unsubstituted indole by the enzyme, tryptophan synthetase. With the preparation of L‐(3a‐ 13 C)‐ and L‐(6‐ 13 C)tryptophan, we have completed the series of indoles and L‐tryptophans with a stable isotope ( 13 C, 15 N or 2 H) in the aromatic ring. In this paper, we also discuss the NMR parameters of these mono‐isotopically labelled systems.