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 C-13(6)-labeled analogues. In this paper, we describe the synthesis of four C-13(6)-labeled THMs, T0-C-13(6), 3,5-T2-C-13(6), TA3-C-13(6), TA4-C-13(6). Starting with C-13(6)-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. (C) 2020 Published by Elsevier Ltd.