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Microbial oxidation of ebastine
H Schwartz1, A Liebig-Weber, H Hochstätter
1Pharmaceutical Research, E. Merck, Med Chem Bioorganica, Darmstadt, Germany.
Applied Microbiology and Biotechnology
|February 1, 1996
Summary
Microbial oxidation of ebastine to carebastine was achieved using Cunninghamella blakesleeana. Optimized conditions increased yield to 40%, demonstrating scalability for carebastine production.
Area of Science:
- Microbiology
- Biotechnology
- Organic Chemistry
Background:
- Ebastine is an antihistamine drug.
- Microbial biotransformation offers a sustainable route for drug metabolite synthesis.
- Carebastine is the active carboxylic acid metabolite of ebastine.
Purpose of the Study:
- To investigate the microbial oxidation of ebastine to carebastine.
- To identify microorganisms capable of this biotransformation.
- To optimize culture conditions for maximizing carebastine yield.
Main Methods:
- Screening of 15 microorganisms for ebastine oxidation.
- Cultivation of Cunninghamella blakesleeana under optimized conditions.
- Analysis of reaction products using Thin Layer Chromatography (TLC), High-Performance Liquid Chromatography (HPLC), Mass Spectrometry (MS), and Nuclear Magnetic Resonance (NMR).
Main Results:
- Cunninghamella strains, particularly Cunninghamella blakesleeana, demonstrated effective microbial oxidation of ebastine to carebastine.
- Optimized culture conditions (200 mg/l substrate, pH 5.0, 1% poly(vinyl alcohol)) increased yield from 10% to 40%.
- Scalable fermentation yielded 270 mg of carebastine from 600 mg ebastine in a 3-L fermenter.
Conclusions:
- Cunninghamella blakesleeana is a suitable microorganism for the biotransformation of ebastine to carebastine.
- Optimized fermentation conditions significantly enhance the yield and efficiency of carebastine production.
- This microbial oxidation method provides a viable and scalable approach for synthesizing carebastine.