摘要
目的制备左沙丁胺醇盐酸盐，并对拆分后得到的S一沙丁胺醇进行外消旋化。方法光学拆分剂L-酪氨酸与外消旋沙丁胺醇形成非映异构体盐，利用两者在甲醇-乙酸乙酯（1：2）溶剂体系中溶解度的差异，完成两者的分离。去除L-酪氨酸后，分别得到R-和S-沙丁胺醇。左沙丁胺醇经过酸化，得到左沙丁胺醇盐酸盐。同时，在1mol·L^-1硫酸溶液，80-90℃条件下，S-沙丁胺醇被外消旋化。结果拆分法得到左沙丁胺醇盐酸盐光学纯度99．1％（ennatiomer excess，EE），总收率为38，7％。S-沙丁胺醇经过外消旋化反应由85．5％EE转变为10．2％EE，收率83．0％。结论通过消旋化作用，S-沙丁胺醇产物可以重新回收利用，能大幅度提高左沙丁胺醇的收率，降低成本，该方法具有广阔的工业化前景。
OBJECTIVE To prepare levalbuterol hydrochloride and make S-salbuterol racemized after the resolution. METHODS The racemic salbuterol and optical resolving agent L-tyrosine were interacted to the formation of diastereomer salt. In the methanol-ethyl acetate （ 1： 2） solvent system, two diastereomer salts were separated by their solubility differences, and after the re- move of L-tyrosine, R-and S-salbuterol were obtained respectively. After acidification, levalbuterol chloride was prepared. Meanwhile, S-salbuterol was racemized at 80 - 90 ℃ in 1 mol · L^- 1 sulfuric acid solution. RESULTS Levalbuterol chloride was 99. 1% EE. And the total yield was 38.7%. S-salbuterol changed from the 85. 5% EE to 10. 2% EE after racemic reaction and the yield was 83.0%. CONCLUSION By the racemization, S-salbuterol can be recycled substantially, increasing the yield of levalbuterol and lowering costs. This method has cheerful prospects for industrialization.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2007年第21期1668-1669,共2页
Chinese Pharmaceutical Journal
关键词
左沙丁胺醇
拆分
外消旋化
制备
levalbuterol
resolution
racemization
preparation
作者简介
王凯，男，讲师
通讯作者：巨修练，男，教授，博士生导师Tel：（027）62108255 E—mail：xiulianju2008@yahoo．com.cn
