Progress Towards Regioselective Nucleophilic Ring Openings of Aziridines

Thyroxine (T4), the predominant secretion of the thyroid gland, undergoes deiodination at target tissues to produce the potent agonist triiodothyronine (T3). Recent work has shown that in vivo enzymatic deiodination and decarboxylation of T3 generates the derivative T1AM, a potent agonist of trace amine associated receptors (TAAR). Interestingly, T1AM induces physiological effects opposite of those produced by the T3 and T4 hormones. Elucidation of a regulatory pathway has the potential to establish more comprehensive treatment options for thyroid-related disorders. Our current focus is on the development of conformationally biased analogs of T1AM as regulators of TAAR activity. This project presents the progress towards regioselective nucleophilic ring openings on aziridines using p-methoxy phenol in the synthesis of proposed TAAR1 regulators and describes a parallel computational study seeking to gain a greater understanding of this key transformation