一种Voxelotor衍生物的合成  

Synthesis of A Voxelotor Derivative

作　　者：王艳娇[1] 徐小娜 高艳蓉 朱周静 唐文强 WANG Yanjiao;XU Xiaona;GAO Yanrong;ZHU Zhoujing;TANG Wenqiang(Xianyang Key Laboratory of Molecular Imaging and Drug Synthesis,School of Pharmacy,Shaanxi Institute of International Trade&Commerce,Xianyang 712046,China;School of Pharmaceutical&Chemical Engineering,Xianyang Polytechnic Institute,Xianyang 712000,China)

机构地区：[1]陕西国际商贸学院医药学院,咸阳市分子影像与药物合成重点实验室,陕西咸阳712046 [2]咸阳职业技术学院医药化工学院,陕西咸阳712000

出　　处：《化学与生物工程》2024年第5期56-59,63,共5页Chemistry & Bioengineering

基　　金：陕西省教育厅专项科研计划项目(23JK0323);咸阳市分子影像与药物合成重点实验室项目(2021QXNL-PT-0008)。

摘　　要：以沃塞洛托(Voxelotor,2)为原料,通过亲核加成、氧化等2步反应,得到Voxelotor衍生物2-羟基-6-((2-(1-异丙基-1H-吡唑-5-基)吡啶-3-基)甲氧基)苯基丙-2-烯-1-酮(1),通过1HNMR和ESI-MS对中间体4及目标化合物1的结构进行了表征,并对中间体4及目标化合物1的合成条件进行了优化。结果表明,最佳亲核加成反应条件为:物料比n(乙烯基溴化镁)∶n(2)为2.0∶1、反应时间为2 h,在此条件下,中间体4收率为62%;最佳氧化反应条件为:反应溶剂为二氯甲烷、氧化剂2-碘酰基苯甲酸(IBX)用量n(IBX)∶n(4)为1.2∶1、反应时间为22 h,在此条件下,目标化合物1收率为54%。Using Voxelotor(2)as a starting material,we obtained Voxelotor derivative 2-hydroxy-6-((2-(1-isopropyl-1 H-pyrazol-5-yl)pyridin-3-yl)methoxy)phenylpropyl-2-ene-1-one(1)through a two-step reaction of nucleophilic addition and oxidation.Moreover,we characterized the structures of intermediate 4 and target compound 1 by 1 HNMR and ESI-MS,and optimized the synthesis conditions of intermediate 4 and target compound 1.The results show that the yield of intermediate 4 can reach 62%under the optimal nucleophilic addition reaction conditions as follows:the material ratio of n(vinylmagnesium bromide)∶n(2)is 2.0∶1,and the reaction time is 2 h.In addition,the yield of target compound 1 can reach 54%under the optimal oxidation reaction conditions as follows:dichloromethane is adopted as the reaction solvent,the dosage of oxidant 2-iodoacyl benzoic acid(IBX)n(IBX)∶n(4)is 1.2∶1,and the reaction time is 22 h.

关 键 词：沃塞洛托 衍生物 亲核加成反应 氧化反应 

分 类 号：O625.6[理学—有机化学]