摘要
报道了一种斑蝥素的常压合成方法。以3-氧代-4-甲酸甲酯四氢噻吩为起始原料,经氰基化和腈醇脱水反应制得3-氰基-4-甲酸甲酯-2,5-二氢噻吩(1);1水解制得2,5-二氢噻吩-3,4-二羧酸(2);2在二氯亚砜作用下脱水制得关键中间体2,5-二氢噻吩-3,4-二羧酸酐(3);3依次经D-A反应和Raney Ni催化加氢的脱硫反应合成了斑蝥素(5),总收率38%,其结构经1H NMR,13C NMR和MS(ESI)确证。研究了离子液体、反应时间和反应温度对D-A反应的影响。确定D-A反应的较优条件为:[BMIM]·BF4为离子液体,于35℃反应20 h,斑蝥素前体产率为86%。
A synthesis method of cantharidin was reported. 3-Cyano-4-carbomethoxy-2,5-dihydrothiophene( 1) was obtained by cyanation and dehydration,using 3-oxo-4-carbomet-hoxy-tetrahydrothiophene as the starting material. 2,5-Dihydrothiophene-3,4-dicarboxylic acid( 2) was prepared by hydrolysis reation of 1. The key intermediate 2,5-dihydrothiophene-3,4-dicarboxylic acid anhydride( 3)was achieved by dehydration reaction of 2 in the presence of SOCl_2. Cantharidin was synthesized by D-A reaction and Raney Ni catalyzed desulfurization with total yield of 38%. The structure was confirmed by1 H NMR,13 C NMR and MS( ESI). Effects of ionic liquid,reaction time and temperature on the D-A reation were investigated as well. The results showed that the optimum conditions were as follows: [BMIM]·BF4 as ionic liquid,reaction at 35 ℃ for 20 h. The yield of cantharidin precursor was 86%.
出处
《合成化学》
CAS
CSCD
北大核心
2018年第2期140-143,共4页
Chinese Journal of Synthetic Chemistry
基金
重庆市科委应用开发计划项目(cstc2014yykf C10004)
