Resolution of Rac-Bambuterol via Diastereoisomeric Salt Formation with o-Chloromandelic Acid and Differences in the Enantiomers' Pharmacodynamical Effects in Guinea Pigs and Beagles.
作者信息
Wu Jie, Liu Fei, Wang Shanping, Wang Hongjun, Liu Qing, Song Xinghan, Li Junxiao, Xu Ling, Tan Wen
机构信息
School of Bioscience and Bioengineering, South China University of Technology; Pre-Incubator for Innovative Drug and Medicine, South China University of Technology; Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, South China University of Technology, Guangzhou, Guangdong, China.
Keypharma Biomedical Inc., Songshan Lake Science & Technology Industry Park, Dongguan, Guangdong, China.
出版信息
Chirality. 2016 Apr;28(4):306-12. doi: 10.1002/chir.22573. Epub 2016 Jan 25.
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.
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