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。
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.
作者
刚丽霞
张道明
张荣震
李达
盛荣
GANG Lixia;ZHANG Daoming;ZHANG Rongzhen;LI Da;SHENG Rong(College of Pharmaceutical Sciences of Zhejiang University,Hangzhou 310058,China;Zhejiang East-Asia Pharmaceutical Co.,Ltd.,Taizhou 317100,China;Shanghai RightHand PharmTech Co.,Ltd.,Shanghai 201318,China)
出处
《中国现代应用药学》
CAS
CSCD
北大核心
2024年第15期2066-2070,共5页
Chinese Journal of Modern Applied Pharmacy
