| 引用本文: | 刚丽霞,张道明,张荣震,李达,盛荣.拉诺康唑的合成工艺研究[J].中国现代应用药学,2024,41(15):1-5. |
| GANG Lixia,ZHANG Daoming,ZHANG Rongzhen,LI Da,SHENG Rong.Study on the Synthetic route of Lanoconazole[J].Chin J Mod Appl Pharm(中国现代应用药学),2024,41(15):1-5. |
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| 摘要: |
| 目的 研究咪唑类抗真菌药物拉诺康唑(1)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(2)、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 路线总收率为36.7%(以邻氯扁桃酸计),各步关键中间体及目标物结构经MS 和1HNMR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。 |
| 关键词: 拉诺康唑 咪唑类抗真菌药物 合成工艺 |
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| Study on the Synthetic route of Lanoconazole |
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GANG Lixia1, ZHANG Daoming2, ZHANG Rongzhen2, LI Da2, SHENG Rong3
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1.Zhejiang East-Asia Pharmaceutical Co., Ltd.;2.Shanghai RightHand PharmTech Co., Ltd.;3.Zhejiang University
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| Abstract: |
| ABSTRACT: OBJECTIVE To study the the synthetic process of imidazole antifungal drug Lanoconazole (1). METHODS Lanoconazole (1) 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, which was cyclized the reaction ofhen configuration conversion, separation and recrystallization. RESULTS The total yield of this route was 36.7% 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. |
| Key words: Lanoconazole imidazole antifungal drug synthetic route |
