J. Wilkinson
Aug 1, 1956
Citations
0
Influential Citations
13
Citations
Journal
The Biochemical journal
Abstract
Interest in the acetic acid analogues* of thyroxine [3:5 diiodo 4 (4'hydroxy 3':5' diiodophenoxy)phenylacetic acid] and triiodothyronine [3:5-diiodo4-(4'-hydroxy-3'-iodophenoxy)phenylacetic acid] has been stimulated by the observations ofThibault & Pitt-Rivers (1955), who demonstrated that both substances produced an immediate rise in the rate of oxygen consumption of rat-kidney slices and, at certain dose levels, in the basal metabolic rate of thyroidectomized rats. When tested in rats both substances had previously been shown to exert thyroxine-like activity, results which led PittRivers (1953) to suggest that there is strong presumptive evidence that these compounds may play a part in the metabolism of the thyroid hormone. Trotter (1955) showed that triiodothyroacetic acid produced a beneficial effect in human myxoedema, though attempts to demonstrate an immediate rise in the basal metabolic rate were inconclusive. As a supply of these substances was required for investigation by a number of techniques applied to other analogues of thyroid hormones in these laboratories, a study has been made of their methods of preparation. Diiodothyroacetic acid and the tetraiodo-compound were originally prepared by Harington & Pitt-Rivers (1952), and Pitt-Rivers (1953) subsequently obtained the triiodo compound by partial iodination of the diiodo derivative. The starting material used by these authors was the relatively inaccessible 3:5-diiodo-4-(4'-methoxyphenoxy)benzaldehyde, but the synthesis of thyroxine by Borrows, Clayton & Hems (1949) suggested a more convenient preparative route for the required compounds. p-Hydroxyphenylacetic acid was nitrated and the dinitro-derivative converted into its ethyl ester (I). The toluene-p-sulphonyl derivative of the ester reacted in anhydrous pyridine with p-methoxy-