Synthesis of Tritium-labelled Tyrosine, 3 : 5-Diiodotyrosine and Thyroxine

Abstract

ALTHOUGH much of the progress in thyroid hormone biochemistry is due to the use of thyroxine and 3 : 5 : 3′-triiodothyronine labelled with iodine-131, the high metabolic lability of the iodine atoms makes it impossible to follow the fate of these substances beyond the stage of enzymic deiodination¹. The low specific activity of thyroxine labelled with carbon-14² has ruled out its use under physiological conditions. Hence, with the availability of pure tritium gas and methods for its measurement, it was decided to prepare tritium-labelled thyroxine. The commonly used methods of exchange could not be used because of the danger of reductive deiodination by tritium gas. The procedure summarized below, and which involved the synthesis of N-acetyl-tyrosine and N-acetyl-3 : 5-diiodotyrosine as intermediates, was finally adopted. All compounds were hence labelled in 2 carbon atoms of their alanine side-chain.