Asymmetric Synthesis of the Carbon-14-Labeled Selective Glucocorticoid Receptor Modulator using Cinchona Alkaloid Catalyzed Addition of 6-Bromoindole to Ethyl Trifluoropyruvate

We describe in this study the asymmetric synthesis of radioisotope (RI)-labeled selective glucocorticoid receptor modulator. This synthesis is based on optimization of the cinchona alkaloid catalyzed addition of 6-bromoindole to ethyl trifluoropyruvate and Negishi coupling of zinc cyanide to the 6-b...

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Detalles Bibliográficos
Autores principales: Sumiyoshi, Takaaki, Urabe, Daisuke, Tojo, Kengo, Sakamoto, Masato, Niidome, Kazumi, Tsuboya, Norie, Nakajima, Tomoko, Tobe, Masanori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2012
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268165/
https://www.ncbi.nlm.nih.gov/pubmed/22728350
http://dx.doi.org/10.3390/molecules17066507
Descripción
Sumario:We describe in this study the asymmetric synthesis of radioisotope (RI)-labeled selective glucocorticoid receptor modulator. This synthesis is based on optimization of the cinchona alkaloid catalyzed addition of 6-bromoindole to ethyl trifluoropyruvate and Negishi coupling of zinc cyanide to the 6-bromoindole moiety. [(14)C] Labeled (−)-{4-[(1-{2-[6-cyano-1-(cyclohexylmethyl)-1H-indol-3-yl]-3,3,3-trifluoro-2-hydroxypropyl}piperidin-4-yl)oxy]-3-methoxyphenyl}acetic acid (−)-1 was synthesized successfully with high enantioselectivity (>99% ee) and sufficient radiochemical purity.

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