Synthesis of indoles and L‐tryptophans specifically ²H‐ or ¹³C‐labelled in the six‐membered ring

Abstract (4‐ 2 H)‐, (5‐ 2 H)‐, (6‐ 2 H)‐, (7‐ 2 H)‐, (4‐ 13 C)‐ and (5‐ 13 C)‐1 H ‐indole and the corresponding six L‐tryptophans [(4‐ 2 H)‐, (5‐ 2 H)‐, (6‐ 2 H)‐, (7‐ 2 H)‐, (4‐ 13 C)‐ and (5‐ 13 C)‐] have been synthesized from simple labelled starting materials via a single reaction scheme. The L‐tryptophans were prepared from the indoles via a quantitative one‐step biosynthetic conversion. A scheme leading to the synthesis of three other indoles, mono‐ 13 C‐enriched in the six‐membered ring, has been developed and optimized. Indole and L‐tryptophan, 13 C‐ or 2 H‐enriched at the positions 4 or 5, have been synthesized with 99% isotope incorporation without scrambling. (6‐ 2 H)‐1 H ‐Indole and ‐tryptophan have been synthesized with 95% deuterium incorporation and (7‐ 2 H)‐1 H ‐indole and ‐tryptophan with 96%. The reactions have been carried out on a gram scale and, in the case of the 4‐ 13 C system, they have been scaled up to the ten‐gram level with no deterioration in yield.