Jeremy Whitmore ACF Abstract FY12

"Regioselective Nucleophilic Ring Opening of Aziridines in the Synthesis of T1AM Analogues"

243rd American Chemical Society (ACS) Spring 2012 National Meeting

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. Interestingly, T1AM induces physiological effects opposite to those produced by the T3 and T4 hormones (Scanlan et al. 2004). Presently, a regulatory relationship between T1AM and the thyroid hormones requires a more fundamental understanding of the TAAR1 receptor and its ligands. Elucidation of a regulatory pathway has the potential to establish more comprehensive treatment options for thyroid-related disorders. Previous work by this lab has shown agonist/antagonist regulation of TAAR1 using the two enantiomers of apomorphine. Herein, this project describes the regioselectivity of nucleophilic ring openings on aziridines using p-methoxy phenol and presents the progress towards the synthesis of a proposed TAAR1 regulator.