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

Autor: Norie Tsuboya, Masanori Tobe, Tomoko Nakajima, Kazumi Niidome, Masato Sakamoto, Kengo Tojo, Daisuke Urabe, Takaaki Sumiyoshi
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: Molecules, Vol 17, Iss 6, Pp 6507-6518 (2012)
Druh dokumentu: article
ISSN: 1420-3049
DOI: 10.3390/molecules17066507
Popis: 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.
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