4-(3-羟基丁氧基)-2-丁醇光学异构体的合成

Synthesis of Three Stereoisomers of 4-( 3-Hydroxylbutoxy)-2-butanol

以廉价易得的(R/S)-3-羟基丁酸甲酯(4a/4b)为起始原料,经过5步反应,以44%~50%的总收率合成了4-(3-羟基丁氧基)-2-丁醇光学异构体1a^1c,为相应的手性新药的开发提供了新途径.

Dihydroxydibutylether（ DHBE） is a choleretic drug used for the treatment of gallstone and hepatic disorders due to its choleretic activity and hepatoprotective action. 4-（ 3-Hydroxylbutoxy）-2-butanol（ 1） is one of the three stereoisomers of DHBE. The compound has rapid efficacy in the body. It contains three stereoisomers,（ R）-4-[（ R）-3-hydroxybutoxy]-2-butanol（ 1a）,（ S）-4-[（ S）-3-hydroxybutoxy]-2-butanol（ 1b） and（ R）-4-[（ S）-3-hydroxybutoxy]-2-butanol（ 1c）. In this paper,the synthesis of the three stereoisomers of compound 1 from readily available starting materials,methyl（ R / S）-3-hydroxybutanoate,in 5 steps with overall yields of 44%—50% was reported. The ether was synthesized by Williamson reaction first,followed by the removal of the benzyl. Then the target compounds 1a—1c were obtained. The synthetic approach has the advantages of easy manipulation,high yield and purity.