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本研究对奥贝胆酸(1)的合成工艺进行了优化。3α-羟基-7-氧代-5β-胆烷酸(2)经酯化和3-位硅烷化得3α-三甲基硅氧基-7-氧代-5β-胆烷酸甲酯(4)。以三氟甲磺酸三甲基硅基酯代替传统的烯醇化试剂三甲基氯硅烷,在-10℃即可将4完全转化为3α,7-二(三甲基硅氧基)-6-烯-5β-胆烷酸甲酯(5),收率由64.3%提高至98.0%。使用三氟化硼乙腈代替三氟化硼乙醚作羟醛缩合剂,使5与乙醛反应得3α-羟基-6-亚乙基-7-氧代-5β-胆烷酸甲酯(6),收率由70.0%提高至93.2%。6经加氢还原、水解和7-位羰基还原得1。优化后的工艺操作简便,反应条件温和,成本低,总收率由24.6%提高至73.6%(以2计)。
In this study, the synthesis of acylacic acid (1) was optimized. 3α-hydroxy-7-oxo-5β-cholanoic acid (2) Methyl 3α-trimethylsiloxy-7-oxo-5β-cholenoate (4 ). Conversion of 4 to 3α, 7-bis (trimethylsiloxy) -6 (trimethylsilyl) -3-methyl-3- -en-5β-cholenoic acid methyl ester (5), the yield increased from 64.3% to 98.0%. Using boron trifluoride acetonitrile instead of boron trifluoride etherate as aldol condensing agent, reacting 5 with acetaldehyde to obtain methyl 3α-hydroxy-6-ethylidene-7-oxo-5β-cholenoate (6) , The yield increased from 70.0% to 93.2%. 6 by hydrogenation, hydrolysis and 7-carbonyl reduction of 1. The optimized process is simple, mild reaction conditions, low cost, the total yield increased from 24.6% to 73.6% (2).