正交试验优化他达拉非合成过程中Pictect-Spengler反应  

Optimizing the Pictect-Spengler reaction in tadalafil synthesis by orthogonal test

作　　者：宋泽文 牟帅儒 赵浩彤 苏佳佩 安仁波[1] 梁承武 SONG Zewen;MOU Shuairu;ZHAO Haotong;SU Jiapei;AN Renbo;LIANG Chengwu(School of Pharmacy,Yanbian University,Yanji,Jilin Province,133002;School of Pharmacy,Jilin Medical University,Jilin City,Jilin Province,132013,China)

机构地区：[1]延边大学药学院,吉林延吉133002 [2]吉林医药学院药学院,吉林吉林132013

出　　处：《吉林医药学院学报》2019年第5期329-331,共3页Journal of Jilin Medical University

基　　金：2016年大学生创新创业项目(2016C307)

摘　　要：目的 通过正交试验方法优化他达拉非合成过程中Pictect-Spengler反应。方法 选择异丙醇作为溶剂,获得较好的立体选择性,通过单因素实验考察胡椒醛的当量、反应温度和反应时间对产率的影响,并用正交设计的实验方法确定最佳的合成条件。结果 他达拉非合成过程中Pictect-Spengler反应的最佳的合成条件为:胡椒醛1.3当量、反应温度86℃、反应时间5h,此时产率为91.50%,熔点为238.6℃,并其三种条件对目标产物产率均有显著影响(P<0.01)。结论 3个因素对他达拉非合成过程中影响最大的条件为温度,并与正交实验之前相比产率升高。Objective To optimize the Pictect-Spengler reaction in the synthesis of tadalafil by orthogonal test. Methods Isopropanol was selected as the solvent to get better stereoselectivity.The effects of piperonal yield,reaction temperature and reaction time on yield were investigated by single factor experiment.The optimum synthesis conditions were determined by orthogonal design. Results The optimized synthesis condition was 1.3 quivalent piperonal,reaction temperature was 86 ℃,reaction time lasted 5 h,melting point was 238.6 ℃ and the yield was 91.50%. Conclusion The factor which exerts the greatest influence on the synthesis of tadalafil is temperature,and the yield is increased than before.

关 键 词：他达拉非 Pictect-Spengler反应 正交优化 

分 类 号：R914.5[医药卫生—药物化学]