Chasing the Elusive Benzofuran Impurity of the THR Antagonist NH-3: Synthesis, Isotope Labeling, and Biological Activity

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• 作者：Latika Singh ; Brandon Pressly ; Brenda J. Mengeling ; James C. Fettinger ; J. David Furlow ; Pamela J. Lein ; Heike Wulff ; Vikrant Singh
• 刊名：Journal of Organic Chemistry
• 出版年：2016
• 出版时间：March 4, 2016
• 年：2016
• 卷：81
• 期：5
• 页码：1870-1876
• 全文大小：398K
• ISSN：1520-6904

文摘

We have synthesized and established the structure of a long-suspected, but hitherto unknown, benzofuran side product (EBI) formed during the synthesis of NH-3. Understanding the mechanism of its formation has enabled isotope (D) labeling. We further developed a highly efficient method for separating EBI from NH-3. Interestingly, EBI was found to be a very potent thyroid hormone receptor (THR) agonist, while NH-3 is an antagonist. In this process, we have also achieved a significantly improved synthesis of NH-3.