拉诺康唑的合成工艺研究

Study on the Synthetic Route of Lanoconazole

摘要:
目的研究咪唑类抗真菌药物拉诺康唑的合成工艺。
方法以邻氯扁桃酸为原料，经酯化、卤代、还原和甲磺酰酯化反应得到化合物4D，4D与1-咪唑基乙腈、二硫化碳、氢氧化钾反应得到二钾盐化合物3，然后经环合、构型转化，并分离纯化和重结晶制得拉诺康唑。
结果总收率为36.5%(以邻氯扁桃酸计)，各步关键中间体及目标物结构经MS 和¹H-NMR确证。
结论该合成工艺操作简便，原料廉价易得，三废较少，适合工业化生产。

Abstract:
OBJECTIVE To study the the synthetic process of imidazole antifungal drug lanoconazole.
METHODS Lanoconazole was synthesized using 2-Chloromandelic acid as the starting material, via esterification, halogenation, reduction, methylsulfonyl esterification to get compound 4D, followed by reaction with 1-imidazolyl acetonitrile, carbon disulfide and potassium hydroxide to get dipotassium salt compound 3, cyclization, configuration conversion, separation and recrystallization to get lanoconazole.
RESULTS The total yield was 36.5% based on 2-Chloromandelic acid. The structures of lanoconazole and key intermediates in the process were confirmed by MS and ¹H-NMR.
CONCLUSION The synthetic process is simple in operation and suitable for industrial production with cheap and readily available raw materials and less waste.