Thyroxine racemization

The primary amino group of the analyte ionizes in the presence of acid and forms ammonium ion (—NH3+). The ammonium ions form strong hydrogen-bondings with the oxygen atoms of CCE. Therefore, the presence of an acid in the mobile phase is essential to achieve the chiral resolution on these CSPs. However, recently, Aboul-Enein et al. [75] observed very interesting results for the chiral resolution of thyroxine and tocainide racemates on the (+)-(18-crown-6)-2,3,ll,12-tetracarboxylic acid CCE. The authors reported the chiral resolution of these molecules without using an acid in the mobile phase. Moreover, they... 

The effect of beta-adrenoceptor antagonists on thyroid hormone metabolism is unlikely to play a significant role in their use in hyperthyroidism. Since D-propranolol has similar effects on thyroxine metabolism to those seen with the racemic mixture, membrane-stabilizing activity may be involved (176). 

Synthetic racemic thyroxine has been resolved and the biological properties of both antipodes, the natural levorotatory (L-T4) and the dextrorotatory D-T4) forms, have been evaluated. L-T4is about 10 times more active than D-T4 [180]. At the present time D-T4 appears to be the only th5n oid analog accepted by some cHnicians as a hypocholesterolemic agent. It is claimed that D-T4 exerts approximately one-twentieth the calorigenic activity of L-T4 in man whereas the cardiac-stimulating activity is purported to be only 1-2% that of L-T4 [181]. 

Evans has developed a direct synthesis of diaiyl ethers while investigating the coupling of functionalized phenolic tyrosine derivatives 96 and 97 [64]. The desired diaryl ethers were obtained in good to excellent yields with pyridine as base and no observed racemization. The thyroxine intermediate 98 was obtained in 81% yield under these conditions using a mixture of pyridine/EtjN (1 1) (5 equiv) as a base (Scheme 3.43). 

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