盐酸左布诺洛尔的合成研究

Synthesis of levobunolol hydrochloride

目的研究青光眼治疗药盐酸左布诺洛尔的合成工艺。方法以1,5-萘二磺酸钠为原料经碱熔法制得1,5-萘二酚,经雷尼镍催化氢化得到5-羟基萘满酮,用环氧氯丙烷醚化,不经分离直接用叔丁胺氨化,最后用右旋酒石酸拆分消旋体得到盐酸左布诺洛尔。结果与结论目标化合物的结构经比旋光度、IR和1H-NMR谱确证。消旋体收率达79%(以5-羟基萘满酮计),拆分率达32%(以消旋体计),光学纯度(ee值)为100%,达到美国药典标准。该合成路线操作简便,成本降低,适合工业化生产。

Aim To synthesize levobunolol hydrochloride. Methods The 5-hydroxy-1-tetralone was prepared from sodium 1,5-naphthalene disulfonate by alkali fusion, and hydrogenation using Raney Ni as catalyst. Then it was converted into racemic bunolol by etherification with epichlorohydrin, and ammonification with tert-butylamine. Finally the target compound was obtained from racemate by optical resolution using d-tartrate. Results and conclusion The target compound was synthesized successfully with low cost （79 % yield from 5-hydroxy-1-tetralon） and high optical purity（ee = 100.% ）, thus the process is suitable for industrial production. The structure of the target compound was identified by IR,optical rotation and ^1H-NMR.