Resolution of Rac‐Bambuterol via Diastereoisomeric Salt Formation with o‐Chloromandelic Acid and Differences in the Enantiomers' Pharmacodynamical Effects in Guinea Pigs and Beagles |
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| Authors: | Jie Wu Fei Liu Shanping Wang Hongjun Wang Qing Liu Xinghan Song Junxiao Li Ling Xu Wen Tan |
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| Institution: | 1. School of Bioscience and Bioengineering, South China University of Technology;2. Pre‐Incubator for Innovative Drug and Medicine, South China University of Technology;3. Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, South China University of Technology, Guangzhou, Guangdong, China;4. Keypharma Biomedical Inc., Songshan Lake Science & Technology Industry Park, Dongguan, Guangdong, China |
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| Abstract: | In this study an enantioseparation method for rac‐bambuterol (5‐(2‐(tert‐butylamino)‐1‐hydroxyethyl)‐1,3‐phenylene bis(dimethylcarbamate)) via diastereoisomeric salt formation with o‐chloromandelic acid was developed. The enantiomeric excess (ee) values and chemical purities of the desired products were confirmed by high‐performance liquid chromatography (HPLC) using chiral stationary phase and reverse‐phase HPLC analyses, respectively. The ee values and the chemical purities both exceeded 99%. Animal experiments showed that (R)‐bambuterol was a potent inhibitor for histamine‐induced asthma reactions. (S)‐bambuterol was ineffective in relaxing the airways. Both enantiomers increased heart rates in beagles. Therefore, replacing rac‐bambuterol with (R)‐bambuterol could be beneficial for asthma patients. Chirality 28:306–312, 2016. © 2016 Wiley Periodicals, Inc. |
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| Keywords: | enantioseparation bambuterol o‐chloromandelic acid enantiomer pharmacodynamical effects |
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