New synthetic routes to thyroid hormone analogs: d6-sobetirome, 3H-sobetirome, and the antagonist NH-3

Abstract

New synthetic routes for the preparation of isotopically labeled versions of thyroid hormone agonist sobetirome were developed using Knochel's iodine–magnesium exchange. A more efficient synthesis of the thyroid hormone antagonist NH-3 was developed from a common intermediate in the sobetirome route. Using the new synthetic routes, d6-and 3H-sobetirome were prepared for their use in studying biodistribution and the cellular uptake of sobetirome. The new route to NH-3 allows for a more rapid and efficient synthesis and provides access to an advanced intermediate to facilitate antagonist analog production in the final bond-forming synthetic step.