Placzek Andrew T, Scanlan Thomas S
Program in Chemical Biology, Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, OR 97239, USA.
Tetrahedron. 2015 Sep 2;71(35):5946-5951. doi: 10.1016/j.tet.2015.05.049. Epub 2015 May 20.
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, d- and H-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.
利用克诺赫尔的碘-镁交换反应，开发了制备甲状腺激素激动剂索贝替罗同位素标记版本的新合成路线。从索贝替罗合成路线中的一个常见中间体出发，开发了一种更高效合成甲状腺激素拮抗剂NH-3的方法。利用这些新合成路线，制备了氘代和氢代索贝替罗，用于研究索贝替罗的生物分布和细胞摄取。通往NH-3的新路线实现了更快速高效的合成，并提供了一种高级中间体，便于在最终的成键合成步骤中生产拮抗剂类似物。
