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DOI: 10.1055/s-2005-921624
Proline-Catalyzed (S)-Oxybutynin Precursor Synthesis
O. Tokuda, T. Kano, W.-G. Gao, T. Ikemoto, K. Maruoka*
Kyoto University, Japan
Publication History
Publication Date:
22 November 2005 (online)
Significance
An organocatalytic synthesis of an (S)-oxybutynin precursor is reported. Oxybutynin (ditropan) is an important drug for the treatment of urinary frequency that so far has been used in racemic form. Because biological studies suggest the (S)-enantiomer to have an improved therapeutic profile its synthesis becomes relevant. Various (S)-2-cyclohexyl-2-phenylglycolic esters were prepared starting from cyclohexanone and phenylglyoxylate derivatives via a proline-catalyzed aldol reaction with good yields and excellent diastereoselectivity and enantioselectivity (dr = 20:1, 96-99% ee). The esters could be converted into (S)-2-cyclohexyl-2-phenylglycolic acid in five steps with an overall yield of 60% and >99% ee after recrystallization. Proline-catalyzed enantioselective intermolecular ketone to ketone aldol reactions have not been described before.