Preparation of antihistamine fexofenadine by bioconversion of terfenadine

摘要

Fexofenadine and its enantiomers (I) are prepared from terfenadine and its enantiomers (II) by bioconversion using a culture of either Absidia corymbifera or of Streptomyces, especially S. platensis, at pH 5.0 - 8.0. Fexofenadine is the racemic mixture of the enantiomers of formula (I): and terfenadine is the racemic mixture of the enantiomers of formula (II): The preferred microorganisms used for the conversion are A. corymbifera LCP 63-1800 or S. platensis NRRL 2364. (II) is preferably added to the culture medium at a concentration of 0.5 - 10g/liter and the mixture is aerated at 1 liter/minute per liter of culture broth, at a temperature of 26 - 28 deg C. (I) is extracted from the broth, preferably using ethyl acetate. Independent claim covers the intermediate (IIIc):