Asymmetric synthesis of the carbon-14-labeled selective glucocorticoid receptor modulator using cinchona alkaloid catalyzed addition of 6-bromoindole to ethyl trifluoropyruvate

Molecules. 2012 May 30;17(6):6507-18. doi: 10.3390/molecules17066507.

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.

MeSH terms

  • Carbon Radioisotopes
  • Catalysis
  • Cinchona Alkaloids / chemistry*
  • Indoles / chemistry*
  • Piperidines / chemistry*
  • Pyruvic Acid / analogs & derivatives*
  • Pyruvic Acid / chemistry
  • Receptors, Glucocorticoid / antagonists & inhibitors*
  • Temperature

Substances

  • (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
  • 6-bromoindole
  • Carbon Radioisotopes
  • Cinchona Alkaloids
  • Indoles
  • Piperidines
  • Receptors, Glucocorticoid
  • ethyl trifluoropyruvate
  • Pyruvic Acid