The microbial oxidation of ebastine to carebastine was investigated. Among the 15 micro-organisms examined, only the Cunninghamella strains showed the desired biotransformation. Cunninghamella blakesleeana oxidised the substrate within 7 days, via the intermediates alcohol and aldehyde, mainly to carebastine, the corresponding carboxylic acid. Optimisation of the culture conditions increased the yield from initially 10% up to a reproducible 40%. For the synthesis of carebastine a substrate concentration of 200 mg/l, a starting pH of 5.0 and the addition of 1% poly(vinyl alcohol) is favourable. The results achieved in experiments with shaking flasks are transferable to the fermentation scale and yielded 270 mg carebastine in a 3-1 fermentation of 600 mg ebastine. The progress of the reaction was detected by TLC and HPLC, the products were identified by mass spectrometry and NMR.

The microbial oxidation of ebastine to carebastine was investigated. Among the 15 micro-organisms examined, only the Cunninghamella strains showed the desired biotransformation. Cunninghamella blakesleeana oxidised the substrate within 7 days, via the intermediates alcohol and aldehyde, mainly to carebastine, the corresponding carboxylic acid. Optimisation of the culture conditions increased the yield from initially 10% up to a reproducible 40%. For the synthesis of carebastine a substrate concentration of 200 mg/l, a starting pH of 5.0 and the addition of 1% poly(vinyl alcohol) is favourable. The results achieved in experiments with shaking flasks are transferable to the fermentation scale and yielded 270 mg carebastine in a 3-1 fermentation of 600 mg ebastine. The progress of the reaction was detected by TLC and HPLC, the products were identified by mass spectrometry and NMR.