Resolution of Rac-Bambuterol via Diastereoisomeric Salt Formation with o-Chloromandelic Acid and Differences in the Enantiomers' Pharmacodynamical Effects in Guinea Pigs and Beagles
详细信息 查看全文
- 作者：Jie Wu ; Fei Liu ; Shanping Wang ; Hongjun Wang ; Qing Liu ; Xinghan Song ; Junxiao Li ; Ling Xu and Wen Tan
- 关键词：enantioseparation ; bambuterol ; o-chloromandelic acid ; enantiomer ; pharmacodynamical effects
- 刊名：Chirality
- 出版年：2016
- 出版时间：April 2016
- 年：2016
- 卷：28
- 期：4
- 页码：306-312
- 全文大小：552K
- ISSN：1520-636X
文摘
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.