A biocatalytic resolution of chiral ketals, intermediates in the synthesis of azole drugs

Crude lipases are used for the resolution of racemic ketals advanced intermediates in the synthesis of cis-terconazole and cis-ketoconazole. Lipase from Aspergillus niger allows to obtain the (2R, 4R)-enantiomer of the imidazole-substituted ketal in good ee at low conversion. The addition of adsorbing resins improves the efficiency to interesting ee values for practical applications. The compound is transformed into (2R, 4S)-terconazole. The survived ester gives access to the other enantiomer.