title: Resolution of Rac-Bambuterol via Diastereoisomeric Salt Formation with o-Chloromandelic Acid and Differences in the Enantiomers' Pharmacodynamical Effects in Guinea Pigs and Beagles.
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.
authors.affiliation: 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.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Shanping
authors.initials: S
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Xinghan
authors.initials: X
authors.lastname: Song
authors.affiliation: 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.
authors.forename: Junxiao
authors.initials: J
authors.lastname: Li
authors.affiliation: Keypharma Biomedical Inc., Songshan Lake Science & Technology Industry Park, Dongguan, Guangdong, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006168:Guinea Pigs; D006632:Histamine / Q000737:chemistry*; D006801:Humans; D008333:Mandelic Acids / Q000737:chemistry*; D013237:Stereoisomerism; D013726:Terbutaline / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C541344:2-chloromandelic acid; D008333:Mandelic Acids; D006632:Histamine; D013726:Terbutaline; C047766:bambuterol
keywords: bambuterol; enantiomer; enantioseparation; o-chloromandelic acid; pharmacodynamical effects