盐酸帕洛诺司琼的合成工艺研究  

Study on the synthesis of Palonosetron hydrochloride

作　　者：陆一菱 马晴 徐敏[1] 兰瑛[1] 刘力超 LU Yiling;MA Qing;XU Min;LAN Ying;LIU Lichao(The Third People’s Hospital of Chengdu,Chengdu,Sichuan,610031 P.R.China;Chengdu Sino-Strong Pharmaceutical Co.,Ltd.,Chengdu,Sichuan,611130 P.R.China)

机构地区：[1]成都市第三人民医院,四川成都610031 [2]成都新恒创药业公司,四川成都611130

出　　处：《华西药学杂志》2021年第3期298-302,共5页West China Journal of Pharmaceutical Sciences

摘　　要：目的研究化疗止吐药盐酸帕洛诺司琼的合成工艺。方法以1,2,3,4-四氢萘甲酸消旋体和S-3-氨基奎宁环胺为起始物料料,经缩合、还原、缩合关环、成盐、重结晶等多步反应制备盐酸帕洛诺司琼。结果制备盐酸帕洛诺司琼的总收率为32%。结论新工艺以1,2,3,4-四氢萘甲酸消旋体原料代替昂贵的手性原料实现手性纯化合物盐酸帕洛诺司琼的制备,避免了手性拆分、降低生产成本的同时,也避免了强碱、高压氢化高危反应,具有原料易得、反应条件温和、操作简便等特点,有很好的工业化实施基础。OBJECTIVE To study the synthesis of the antiemetic Palonosetron hydrochloride(PH).METHODS 1,2,3,4-tetrahydro-1-naphthoic acid and S-3-aminoquinuclidine were employed to synthesize PH via multi-step reactions including reduction,condensation,salification,and recrystallization.RESULTS The target product was obtained with 32%overall yield.CONCLUSION Racemate 1,2,3,4-tetrahydro-1-naphthoic acid instead of expensively S-isomer can be employed to synthesize optically pure PH,and the new development cost-saving synthetic process without chiral resolution step but with mild reaction conditions,simple operation and commercially available materials is suitable for industrial production.

关 键 词：5-HT3受体拮抗剂 止吐药物 盐酸帕洛诺司琼 工艺研究 1 2 3 4-四氢萘甲酸 S-3-氨基奎宁环胺盐酸盐 消旋化 动力学拆分 

分 类 号：R914[医药卫生—药物化学]