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

doi:10.3390/molecules17066507

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Molecules 2012, 17(6), 6507-6518; doi:10.3390/molecules17066507

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

Takaaki Sumiyoshi, Daisuke Urabe, Kengo Tojo, Masato Sakamoto, Kazumi Niidome, Norie Tsuboya, Tomoko Nakajima and Masanori Tobe*

Drug Research Division, Dainippon Sumitomo Pharma Co., Ltd., 33-94 Enoki, Suita, Osaka 564-0053, Japan

* Author to whom correspondence should be addressed.

Received: 27 April 2012; in revised form: 18 May 2012 / Accepted: 21 May 2012 / Published: 30 May 2012

(This article belongs to the Special Issue Organocatalysis)

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Abstract: 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. [¹⁴C] 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.

Keywords: organocatalyst; cinchona alkaloid; asymmetric synthesis; radioisotope labeled compound

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MDPI and ACS Style

Sumiyoshi, T.; Urabe, D.; Tojo, K.; Sakamoto, M.; Niidome, K.; Tsuboya, N.; Nakajima, T.; Tobe, M. Asymmetric Synthesis of the Carbon-14-Labeled Selective Glucocorticoid Receptor Modulator using Cinchona Alkaloid Catalyzed Addition of 6-Bromoindole to Ethyl Trifluoropyruvate. Molecules 2012, 17, 6507-6518.

AMA Style

Sumiyoshi T, Urabe D, Tojo K, Sakamoto M, Niidome K, Tsuboya N, Nakajima T, Tobe M. Asymmetric Synthesis of the Carbon-14-Labeled Selective Glucocorticoid Receptor Modulator using Cinchona Alkaloid Catalyzed Addition of 6-Bromoindole to Ethyl Trifluoropyruvate. Molecules. 2012; 17(6):6507-6518.

Chicago/Turabian Style

Sumiyoshi, Takaaki; Urabe, Daisuke; Tojo, Kengo; Sakamoto, Masato; Niidome, Kazumi; Tsuboya, Norie; Nakajima, Tomoko; Tobe, Masanori. 2012. "Asymmetric Synthesis of the Carbon-14-Labeled Selective Glucocorticoid Receptor Modulator using Cinchona Alkaloid Catalyzed Addition of 6-Bromoindole to Ethyl Trifluoropyruvate." Molecules 17, no. 6: 6507-6518.

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