title: Microbial oxidation of ebastine.
abstract: 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.
authors.affiliation: Pharmaceutical Research, E. Merck, Med Chem Bioorganica, Darmstadt, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Schwartz
authors.forename: A
authors.initials: A
authors.lastname: Liebig-Weber
authors.forename: H
authors.initials: H
authors.lastname: Hochstätter
authors.forename: H
authors.initials: H
authors.lastname: Böttcher
mesh_terms: D001711:Biotransformation; D002090:Butyrophenones / Q000378:metabolism*; D006634:Histamine H1 Antagonists / Q000378:metabolism*; D009090:Mucorales / Q000378:metabolism*; D010084:Oxidation-Reduction; D010880:Piperidines / Q000378:metabolism*
chemical_list: D002090:Butyrophenones; D006634:Histamine H1 Antagonists; D010880:Piperidines; C058251:carebastine; C058249:ebastine