T. Sumiyoshi, K. Tojo, D. Urabe
Jan 31, 2011
Citations
0
Influential Citations
8
Citations
Journal
Tetrahedron-asymmetry
Abstract
Abstract We have successfully synthesized enantiomerically pure (+)- and (−)- tert -butyl 6-cyano-3-[3-ethoxy-1,1,1-trifluoro-2-hydroxy-3-oxopropan-2-yl]-1 H -indole-1-carboxylate (+)- 1 and (−)- 1 , which are key intermediates of non-steroidal glucocorticoid receptor modulators, by employing a cinchona alkaloid catalyzed addition of 6-cyanoindole to ethyl trifluoropyruvate. The optimized method can be applied to large-scale synthesis. Furthermore, using the key intermediates (+)- 1 and (−)- 1 , enantiomerically pure glucocorticoid receptor modulators (+)- 3 and (−)- 3 can be synthesized (>99% ee for both compounds). The glucocorticoid receptor binding affinity was influenced by the stereogenic center at the trifluoromethyl alcohol moiety; compound (−)- 3 showed a higher binding affinity compared to (+)- 3 .