The synthesis of 13C6-labeled l-thyronine, 3,5-diiodothyronine, 3,3′,5-triiodothyroacetic acid and 3,3′,5,5′-tetraiodothyroacetic acid

The effects of thyroid hormone metabolites (THMs) other than T3, rT3 and T4 are largely unknown, partially due to the lack of adequate methods. For adequate analysis, internal standards for all THMs are essential, but unfortunately not commercially available. Reported approaches for the synthesis of T0, 3,5-T2, TA3 and TA4 lack sensitivity and/or are not adaptable for 13C6-labeled analogues. In this paper, we describe the synthesis of four 13C6-labeled THMs, T0-13C6, 3,5-T2-13C6, TA3-13C6, TA4-13C6. Starting with 13C6-bromo-benzene, a short and versatile synthesis route was developed in which the formation of the diphenyl ether by a Chan-Lam coupling reaction was fundamental. [Display omitted] •13C6-labeled thyroid hormone metabolites analogues were synthesized from readily available [13]C6-bromo-benzene.•Preparation of corresponding boronic acids was optimized.•Chan-Lam coupling reaction was used as key step.