左旋沙丁胺醇盐酸盐的合成  

Synthesis of levalbuerol

作　　者：何炜[1] 张邦乐[2] 李晓晔[1] 刘鹏[1] 孙晓莉[1] 张生勇[1] 

机构地区：[1]第四军医大学药学系化学教研室,陕西西安710032 [2]第四军医大学药学系药理教研室,陕西西安710032

出　　处：《中国药物化学杂志》2006年第4期222-225,共4页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(20372083);陕西省科技厅攻关项目(2005K10-G1)

摘　　要：目的研究左旋沙丁胺醇盐酸盐的合成方法。方法以水杨醛和溴乙酰氯为原料经Friedel-Crafts酰基化反应、取代反应合成5-[[(1,1-二甲基乙基)胺基]乙酰基]-2-羟基苯甲醛盐酸盐(4),再经手性铑配合物催化的不对称氢转移反应协同还原得到左旋沙丁胺醇(5),最后与盐酸成盐制得左旋沙丁胺醇盐酸盐(1)。结果与结论以水杨醛计,4步反应总收率为35.6%,对映体过量值达92%,该合成路线易行。目标产物的结构经质谱、红外光谱和核磁共振氢谱确证。Aim To develop a synthesis method for levalbuerol. Methods Friedel-Crafts acylation of salicylaldehyde with bromoaeetyl chloride in the presence of aluminum chloride afforded 5-（bromoaeetyl）-2-hydroxybenzaldehyde （3）. Further treatment via condensation, hydrolysis and salt formation in one bath yielded 5-[ [ （ 1,1-dimethylethyl）amino] aeetyl]-2-hydroxy benzaldehyde hydroehloride（4）. R-（ - ）salbutamol was obtained by ehrial Rh-eomplex catalyzed asymmetric transfer hydrogenation of 4. Then salt formation of R-（ - ）salbutamol afforded levalbuerol. Results and conclusion A facile synthetic route for the target compound was provided through a four-step procedure starting from salieylaldehyde in a total yield of 35.6% with ee up to 92 %, and the structure was elucidated by IR, ^1H-NMR and MS.

关 键 词：药物化学 药物制备 不对称合成 左旋沙丁胺醇盐酸盐 左旋沙丁胺醇 

分 类 号：R914[医药卫生—药物化学]