The constitution and synthesis of thyroxine. J.H. Quastel F.R.S. is Research Professor in the Kinsmen Laboratory of Neurological Research at the University of British Columbia, bancouver, Canada 1977 Published by Elsevier Inc.
CHH(NH2). COO. The object of the present paper is in the first place to offer evidence in support of this suggestion, and in the second place to describe the synthesis of thyroxine itself 2.
The Constitution and Synthesis of Thyroxine. desiodo-thyroxine (NATURE, July 10, 1926,. Chemistry; Drug discovery;).
Page 1 XXIII. CHEMISTRY OF THYROXINE. III. CONSTITUTION AND SYNTHESIS OF THYROXINE. BY CHARLES ROBERT HARINGTON AND GEORGE BARGER. From the Department of Pathological Chemistry, University College Hospital. Medical School, London, and the Department of MediQal Chemistry, Uni- versity qf Edinburgh.
Article: Quantitative observations on thyroxine and allied substances: II. Effects on the oxygen consumption of rats.
This being so, it was apparent that the desired tetra-iodophenyl ethers could only be obtained by the introduction of those two iodine atoms (or other groups which could be substituted by iodine) which were destined to occupy the 3: 5 positons, before the phenyl ether synthesis was carried out.
It was obvious, however, that formidable diffi- Mild Quinol monomethyl ether, to give 3: 5- This nitrile, on boiling with a 171 Page 4 C. R. HARINGTON AND G. BARGER culties were to be expected, since the reduction which would be involved in the synthesis, from this aldehyde, of the corresponding a-aminopropionic acid would be.
This series of experiments, therefore, settled beyond doubt the question of the orientation of the iodine atoms in thyroxine, since it is certain that the last two iodine atoms, introduced into the acid (IV) in alkaline solution, must have entered the ortho positions to the free phenolic group.
Treatment, such as warming the components in pyridine solution, or boiling in acetone with potassium carbonate, resulted only in the recovery of un- changed starting material, whilst more vigorous treatment, with the addition of copper bronze, caused the elimination of the relatively labile iodine atoms.
Admittedly these arguments cannot be regarded as convincing, but further evidence by methods of degradation appeared to be out of the question, and the solution of the problem could therefore only be obtained by synthesis.
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Selected References These references are in PubMed. This may not be the complete list of references from this article. Gaddum JH. Quantitative observations on thyroxine and allied substances: II. Effects on the oxygen consumption of rats.
In other words, iodine atoms (or other replaceable groups) had to be present in the ortho positions either to the halogen atom or to the phenolic group which was to take part in the phenyl ether condensation.
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