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

Presentation Type

Poster/Portfolio

Presenter Major(s)

Chemistry

Mentor Information

Matthew Hart

Department

Chemistry

Location

Kirkhof Center KC 76

Start Date

11-4-2012 9:00 AM

Keywords

Health, Life Science, Physical Science

Abstract

Thyroxine (T4), the primary secretion of the thyroid gland, undergoes deiodination at target tissues to produce the potent agonist Triiodothyronine (T3). Recent work has identified a deiodinated and decarboxylated analog of T3, T1AM, which is a potent agonist of trace amine associated receptors. 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 better understanding of the TAAR1 receptor and its ligands. Elucidation of a regulatory pathway could establish more comprehensive treatment options for thyroid-related disorders. Previous work has shown agonist/antagonist regulation of TAAR1 using the two enantiomers of apomorphine. This project describes the regioselectivity of nucleophilic ring openings on aziridines using p-methoxy phenol and presents the progress towards the synthesis of proposed TAAR1 regulators.

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Apr 11th, 9:00 AM

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

Kirkhof Center KC 76

Thyroxine (T4), the primary secretion of the thyroid gland, undergoes deiodination at target tissues to produce the potent agonist Triiodothyronine (T3). Recent work has identified a deiodinated and decarboxylated analog of T3, T1AM, which is a potent agonist of trace amine associated receptors. 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 better understanding of the TAAR1 receptor and its ligands. Elucidation of a regulatory pathway could establish more comprehensive treatment options for thyroid-related disorders. Previous work has shown agonist/antagonist regulation of TAAR1 using the two enantiomers of apomorphine. This project describes the regioselectivity of nucleophilic ring openings on aziridines using p-methoxy phenol and presents the progress towards the synthesis of proposed TAAR1 regulators.