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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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
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author Sumiyoshi, Takaaki
Urabe, Daisuke
Tojo, Kengo
Sakamoto, Masato
Niidome, Kazumi
Tsuboya, Norie
Nakajima, Tomoko
Tobe, Masanori
author_facet Sumiyoshi, Takaaki
Urabe, Daisuke
Tojo, Kengo
Sakamoto, Masato
Niidome, Kazumi
Tsuboya, Norie
Nakajima, Tomoko
Tobe, Masanori
author_sort Sumiyoshi, Takaaki
collection PubMed
description 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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spelling pubmed-62681652018-12-12 Asymmetric Synthesis of the Carbon-14-Labeled Selective Glucocorticoid Receptor Modulator using Cinchona Alkaloid Catalyzed Addition of 6-Bromoindole to Ethyl Trifluoropyruvate Sumiyoshi, Takaaki Urabe, Daisuke Tojo, Kengo Sakamoto, Masato Niidome, Kazumi Tsuboya, Norie Nakajima, Tomoko Tobe, Masanori Molecules Article 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. MDPI 2012-05-30 /pmc/articles/PMC6268165/ /pubmed/22728350 http://dx.doi.org/10.3390/molecules17066507 Text en © 2012 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Sumiyoshi, Takaaki
Urabe, Daisuke
Tojo, Kengo
Sakamoto, Masato
Niidome, Kazumi
Tsuboya, Norie
Nakajima, Tomoko
Tobe, Masanori
Asymmetric Synthesis of the Carbon-14-Labeled Selective Glucocorticoid Receptor Modulator using Cinchona Alkaloid Catalyzed Addition of 6-Bromoindole to Ethyl Trifluoropyruvate
title Asymmetric Synthesis of the Carbon-14-Labeled Selective Glucocorticoid Receptor Modulator using Cinchona Alkaloid Catalyzed Addition of 6-Bromoindole to Ethyl Trifluoropyruvate
title_full Asymmetric Synthesis of the Carbon-14-Labeled Selective Glucocorticoid Receptor Modulator using Cinchona Alkaloid Catalyzed Addition of 6-Bromoindole to Ethyl Trifluoropyruvate
title_fullStr Asymmetric Synthesis of the Carbon-14-Labeled Selective Glucocorticoid Receptor Modulator using Cinchona Alkaloid Catalyzed Addition of 6-Bromoindole to Ethyl Trifluoropyruvate
title_full_unstemmed Asymmetric Synthesis of the Carbon-14-Labeled Selective Glucocorticoid Receptor Modulator using Cinchona Alkaloid Catalyzed Addition of 6-Bromoindole to Ethyl Trifluoropyruvate
title_short Asymmetric Synthesis of the Carbon-14-Labeled Selective Glucocorticoid Receptor Modulator using Cinchona Alkaloid Catalyzed Addition of 6-Bromoindole to Ethyl Trifluoropyruvate
title_sort asymmetric synthesis of the carbon-14-labeled selective glucocorticoid receptor modulator using cinchona alkaloid catalyzed addition of 6-bromoindole to ethyl trifluoropyruvate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268165/
https://www.ncbi.nlm.nih.gov/pubmed/22728350
http://dx.doi.org/10.3390/molecules17066507
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