中文摘要：

发展一条醛糖还原酶抑制剂非达司他的新合成方法,以价廉、易得的N-苯基马来酰亚胺和对氟苯酚为原料,在碱催化下经Oxo-Michael加成反应、水解、（S）-α-苯乙胺拆分、Friedel-Crafts酰化反应得（S）-6-氟-3,4-二氢-4-氧-2H-1-苯并吡喃-2-羧酸,进一步经Bucherer-Bergs乙内酰脲化反应和氯化4-（4,6-二甲氧基-1,3,5-三嗪-2-基）-4-甲基吗啉盐（DMT-MM）作用下的酰胺化反应得目标物,7步反应总收率22.4%.所有中间体和目标物经1H NMR,13C NMR,HRMS及比旋光度确证并与文献值比较.该方法原料易得、反应条件温和,操作简便,收率良好,产物分离纯化容易,适合大规模制备非达司他.

英文摘要：

A novel method for synthesis of fidarestat, an aldose reductase inhibitor, was developed. The key intermediate （S）-6-fluoro-3,4-dihydro-4-oxo-2H-l-benzopyran-2-carboxylic acid （8） was prepared starting from N-phenylmaleimide and 4-fluorophenol, which are inexpensive and easily available starting materials, via base-catalyzed oxo-Michael addition, hydrolysis, resolution with （S）-a-phenylethylamine and Friedel- Crafts acylation. Subsequently, fidarestat was synthesized from 8 through Bucherer-Bergs hydantonination reaction and amidation by using 4-（4,6-dimethoxy-l,3,5-triazin-2-yl）-4-methyl-morpholinium chloride （DMT-MM） as condensation reagent. The overall yield was about 22.4%. The structures of intermediates and final product were determined by 1H NMR, 13C NMR, HRMS techniques, optical rotation and compari- son with reported data. This method has the advantages of easily available starting materials, simply con- ducted procedures, relatively high yield and easy purification, and is more suitable for scale-up production.